Cohn LA, Norris CR, Hawkins EC, et al. Identification and characterization of an idiopathic pulmonary fibrosis-like condition in cats. J Vet Intern Med 2004;18:632-641.
Interstitial lung diseases are a heterogeneous group of disorders with a variety of causes. In veterinary medicine, such lung diseases with a prominent fibrotic component of unknown etiology are often called idiopathic pulmonary fibrosis (IPF). In human medicine, this term is reserved for a distinct disease entity with specific histologic findings labeled as usual interstitial pneumonia (UIP). We identified 23 cats displaying histologic criteria of UIP The purpose of this retrospective study is to describe the presentation and response to therapy of these cats to better define this disease entity. All but 2 cats were middle aged to older (median 8.7 years), with no apparent sex or breed predisposition. Complaints included respiratory distress (n = 18) and cough (13). Duration of signs was less than 6 months in 17 cats. Physical-examination abnormalities included tachypnea, inspiratory or mixed inspiratory and expiratory effort, and adventitial lung sounds. No consistent hematologic or biochemical abnormalities, parasites, or positive serologic results for feline retroviruses, heartworms, or toxoplasmosis were present. Radiographic changes included dense patchy or diffuse interstitial, bronchiolar, and alveolar infiltrates. Analysis of bronchial lavage fluid revealed mild neutrophilic inflammation (n = 6) with no consistent pathogen growth. Clinical condition of 5 cats worsened after lavage. Coincident pulmonary neoplasia was identified in 6 cats. Response to therapy (corticosteroids, antibiotics, bronchodilators, and diuretics) was poor, and most cats died within days to months. Cats with histologic changes compatible with UIP had signs that mimicked many of the clinical findings of human IPF, and treatment response was similarly unrewarding.
Williams K, Malarkey D, Cohn L, et al. Identification of spontaneous feline idiopathic pulmonary fibrosis: morphology and ultrastructural evidence for a type II pneumocyte defect. Chest 2004;125:2278-2288.
STUDY OBJECTIVES: Idiopathic pulmonary fibrosis (IPF) is a poorly understood chronic respiratory disease of humans, which has no correlate in other animals. Understanding the role that inflammation, alveolar epithelial cells, and myofibroblasts play in the progression of the disease is controversial, and hampered by the lack of an animal model. We have identified spontaneous IPF in domestic cats and hypothesized that this newly identified disease shares the pathology of human IPF; further, this work provides data suggesting that the disease is related to a defect in type II pneumocyte biology. SETTING AND SUBJECTS: Chronic respiratory disease with pathology consistent with usual interstitial pneumonia (UIP) spontaneously developed in 16 domestic cats. RESULTS: The histopathology of feline IPF consisted of the following: (1) interstitial fibrosis with fibroblast/myofibroblast foci, (2) honeycombing with alveolar epithelial metaplasia and type II pneumocyte hyperplasia, and (3) alveolar interstitial smooth-muscle metaplasia. Interstitial inflammation was not a prominent feature of the disease. alpha-Smooth muscle actin-positive myofibroblasts were prominent in myofibroblast foci, beneath honeycomb and hyperplastic epithelium, and in alveolar septa away from the remodeling. Feline IPF type II pneumocyte ultrastructure is similar to a heritable form of human IPF, with abnormal cytoplasmic lamellar body-like inclusions. CONCLUSIONS: We conclude the following: (1) chronic respiratory disease with clinical and pathology features of UIP/IPF occurs in the domestic cat; (2) as in human IPF, the type II pneumocyte and myofibroblasts are important cellular constituents of feline IPF; and (3) type II cell ultrastructure suggests feline IPF is a defect in the type II pneumocyte.
Le Boedec K, Roady PJ, O’Brien RT. A case of atypical diffuse feline fibrotic lung disease. J Feline Med Surg 2014;16:858-863.
An 11-year-old cat presented for respiratory distress and weight loss. Thoracic radiographs were interpreted as a diffuse bronchointerstitial pattern with bronchiectasis and a mild ventral alveolar pattern on the lateral views. Computed tomography revealed a severe diffuse reticular pattern, relatively hyperattenuating in subpleural regions, with diffuse traction bronchiectasis and some degree of honeycombing. Despite the absence of basal predominance, this pattern was considered to be suggestive of usual interstitial pneumonia (UIP). Other differentials (other types of interstitial lung disease, infectious pneumonitis, neoplasia, or early edema or hemorrhage) were considered less likely based on history and other test results. The cat was discharged without any treatment, and euthanased 5 months later. Post-mortem histological analysis of the lung revealed end-stage lung, with extensive fibrosis that was more severe in subpleural regions, fibroblastic foci and honeycombing, suggestive of UIP. A probable diagnosis of idiopathic pulmonary fibrosis (IPF) was made. The diffuse distribution of the lesions was atypical compared with previous tomographic and histologic descriptions of IPF in cats. This case report suggests a heterogeneity of the pulmonary fibrotic disorders in cats that warrants further investigation for better characterization and classification.
Roman J, Brown KK, Olson A, et al. An official American thoracic society workshop report: comparative pathobiology of fibrosing lung disorders in humans and domestic animals. Ann Am Thorac Soc 2013;10:S224-229.
BACKGROUND: The clinical outcome of idiopathic pulmonary fibrosis (IPF) is poor, with a 50% survival rate at 3 years. Furthermore, current treatments provide little amelioration of symptoms. Despite significant advances in understanding the clinical features and pathobiology of IPF, further advances have been hampered by a lack of suitable animal models of the disease. Interestingly, spontaneously occurring disorders with a similarity to IPF have been recognized in the dog, cat, horse, and donkey. These disorders share clinical and pathologic features with human IPF and are emerging diseases of veterinary importance. PURPOSE: To improve awareness about these disorders in domestic animals and stimulate interactions between disciplines, and to facilitate the elucidation of mechanisms of fibrosing lung disorders using a comparative natural-occurrence disease model approach. METHODS: A 1-day meeting joined physicians, veterinarians, pathologists, researchers, and advocacy experts to discuss information available in this area. A review of the literature was conducted, and an executive committee discussed the findings and prepared a summary statement during subsequent meetings. RESULTS: Clinical, diagnostic, and treatment opportunities were identified, and common areas of interest where collaborative efforts could accelerate discovery regarding etiological factors, methods for early detection, determinants of disease progression, and novel therapies were defined. CONCLUSIONS: Comparing fibrosing lung disorders in humans and domestic animals will allow for a better understanding of the similarities and differences among species and may offer novel insights into the underlying mechanisms of spontaneously occurring fibrotic lung diseases.
Tashiro J, Rubio GA, Limper AH, et al. Exploring Animal Models That Resemble Idiopathic Pulmonary Fibrosis. Front Med (Lausanne) 2017;4:118. （PDFあり）
Large multicenter clinical trials have led to two recently approved drugs for patients with idiopathic pulmonary fibrosis (IPF); yet, both of these therapies only slow disease progression and do not provide a definitive cure. Traditionally, preclinical trials have utilized mouse models of bleomycin (BLM)-induced pulmonary fibrosis-though several limitations prevent direct translation to human IPF. Spontaneous pulmonary fibrosis occurs in other animal species, including dogs, horses, donkeys, and cats. While the fibrotic lungs of these animals share many characteristics with lungs of patients with IPF, current veterinary classifications of fibrotic lung disease are not entirely equivalent. Additional studies that profile these examples of spontaneous fibroses in animals for similarities to human IPF should prove useful for both human and animal investigators. In the meantime, studies of BLM-induced fibrosis in aged male mice remain the most clinically relevant model for preclinical study for human IPF. Addressing issues such as time course of treatment, animal size and characteristics, clinically irrelevant treatment endpoints, and reproducibility of therapeutic outcomes will improve the current status of preclinical studies. Elucidating the mechanisms responsible for the development of fibrosis and disrepair associated with aging through a collaborative approach between researchers will promote the development of models that more accurately represent the realm of interstitial lung diseases in humans.
コメント：ヒトIPFとの類似性を知るために動物の自然発症の線維症例の情報を集約する研究は、ヒトと動物の両方の研究者にとって有用であることを証明するはずである。今の所、飼育動物（ネコ、イヌなど）における肺線維症の自然発生は有益であり得るが、病因研究および前臨床治療評価のための最も不可欠なモデルはげっ歯類である。 (2019.3.12 代官山動物病院 明石依里子)
Henninger W. Use of computed tomography in the diseased feline thorax. J Small Anim Pract 2003;44:56-64. (PDFあり）
Computed tomography (CT) scanning of the thorax is gaining more attention in veterinary medicine as therapeutic possibilities increase. Plain and contrast-enhanced CT images of the thorax of five referred cats with signs of respiratory disease were evaluated using soft tissue (pleural) and lung windows. The common CT pattern in all cats was involvement of the lung lobes, either as a homogeneous or heterogeneous single lobe hyperdensity. It involved the main bronchus, invaded the cranial or caudal mediastinum, and crossed the border to the opposite lung. Right lung atelectasis and mediastinal shift caused left lung overinflation. Bronchial lymph node enlargement was found unilaterally or bilaterally. CT-guided percutaneous fine needle aspiration biopsy of the lobar lung lesion was performed in four cats; in three cases it revealed carcinoma and in one inflammation, although the cat with suspected inflammation was subsequently found to have a carcinoma on lung lobectomy. Histopathology confirmed lung metastasis in one case and bronchial adenocarcinoma in four cases. A protocol for systematic examination of thoracic CT images is proposed.
コメント：猫における肺腫瘍5例でのCTの有用性についての報告。全ての症例で右葉の病変が認められた。全ての無気肺領域は主気管支を部分的あるいは完全に閉塞していた。全ての肺腫瘍の猫において、リンパ節の腫大あるいは縦隔への浸潤が認められた。病変部のCT値は21~72HUで造影剤投与後には56~120HUまで上昇したが、人で報告されているような特異的なパターンはなかった（兵庫ペット医療センター東灘病院 谷口哲也-2019.3.22 )。
Prather AB, Berry CR, Thrall DE. Use of radiography in combination with computed tomography for the assessment of noncardiac thoracic disease in the dog and cat. Vet Radiol Ultrasound 2005;46:114-121.
Computed tomography (CT) of the thorax was performed in 28 dogs and five cats and findings were compared with previous thoracic radiographs. The sample population included all animals that had thoracic radiographs and a CT study within 5 days of each other, where the complete imaging studies were available for review. Thoracic radiographs were considered indeterminate in 31 patients and CT examinations were done to acquire additional information. The presence of additional information from CT relating to presence of pathology, location of pathology, extent of pathology, and involvement of mediastinal structures was recorded. Whether there was a change in diagnosis based on the CT findings was also recorded. In only 4/33 animals (all dogs) did CT fail to provide any new information for the parameters evaluated when compared with survey thoracic radiographs. Additional information about the pathology that was present was gained by CT in 5/5 cats and 21/ 28 dogs. New information on compartmental location of pathology was seen in 4/5 cats and 19/28 dogs. New information on pathology extent was noted in 5/5 cats and 20/28 dogs. Additional information regarding involvement of mediastinal structures was obtained in 2/5 cats and 10/28 dogs. A change in diagnosis was made in 3/5 cats and 13/28 dogs. In conclusion, CT is a valuable tool for evaluating intrathoracic disease. CT provides additional cross-sectional anatomic information that can aid in anatomic localization and evaluation of the extent of the pathology in question.
Secrest SA, Bailey MQ, Williams KJ, et al. Imaging diagnosis–Feline idiopathic pulmonary fibrosis. Vet Radiol Ultrasound 2008;49:47-50. （PDF）
“The predominant histologic changes shared by cats and humans with idiopathic pulmonary fibrosis include a multifocal distribution of interstitial fibrosis with foci of fibroblast/myofibroblasts, alveolar epithelial metaplasia, interstitial smooth muscle metaplasia/hyperplasia, and a noticeable lack of an inflammatory response. These histologic features, which are referred to as usual interstitial pneumonia, are considered the diagnostic gold standard in humans. There is also a similarity in the ultrastructural features of the type II pneumocyte in feline idiopathic pulmonary fibrosis with that seen in a familial form of human usual interstitial pneumonia, possibly linking the disease to a genetically based type II cell defect.”
Evola MG, Edmondson EF, Reichle JK, et al. Radiographic and histopathologic characteristics of pulmonary fibrosis in nine cats. Vet Radiol Ultrasound 2014;55:133-140.
Pulmonary fibrosis is a progressive fatal interstitial lung disease that is often idiopathic, occurs in multiple species, and may be caused by a number of inciting factors. The purpose of this retrospective, multicenter study was to describe the radiographic and histopathologic characteristics of idiopathic and induced pulmonary fibrosis in a group of cats. Cats with thoracic radiographs and histopathologically confirmed pulmonary fibrosis were recruited using the American College of Veterinary Radiology list serve. A board-certified veterinary radiologist and diagnostic imaging intern reviewed radiographs and recorded characteristics by consensus. Findings from additional imaging modalities were also recorded when available. All histopathology samples were re-reviewed by a veterinary pathology resident. A total of nine cats met inclusion criteria. All patients had a broad range of radiographic characteristics that included broncho-interstitial pattern, alveolar pattern, pulmonary masses, pulmonary bullae, pleural effusion, and cardiomegaly. Cats with available echocardiographic studies had characteristics that included right ventricular dilation and hypertrophy and pulmonary arterial hypertension interpreted to be secondary to primary lung disease. Cats with available CT studies had characteristics that included focally increased soft tissue attenuation, masses, and ventral consolidation that exhibited no improvement with dorsal versus ventral recumbency. Histopathology showed pulmonary fibrosis, type II pneumocyte hyperplasia, and smooth muscle hypertrophy in all patients. Epithelial metaplasia was present only in one patient. Findings from the current study indicated that cats with pulmonary fibrosis have highly variable radiographic characteristics and that these characteristics may mimic other diseases such as asthma, pneumonia, pulmonary edema, or neoplasia.
Skorupski KA, Durham AC, Duda L, et al. Pulmonary fibrosis after high cumulative dose nitrosourea chemotherapy in a cat. Vet Comp Oncol 2008;6:120-125.
Small to intermediate cell alimentary lymphoma was diagnosed in a cat after abdominal exploratory surgery with no prior history of pulmonary disease. Initial response to several chemotherapy regimens was poor, but a long-term remission was achieved with CCNU (lomustine) and corticosteroid therapy. After receiving a total cumulative CCNU dose of 552 mg m(-2) over 12 months, an acute episode of respiratory distress occurred and the cat died. Necropsy identified severe diffuse pulmonary fibrosis and no signs of lymphoma. This is the first report of pulmonary fibrosis following high cumulative dose nitrosourea chemotherapy in a cat.
Pigott AM, Haak CE, Breshears MA, et al. Acute bronchointerstitial pneumonia in two indoor cats exposed to the H1N1 influenza virus. J Vet Emerg Crit Care (San Antonio) 2014;24:715-723.
OBJECTIVE: To describe 2 cases of acute bronchointerstitial pneumonia in indoor domestic cats infected by anthroponotic transmission of pandemic 2009 influenza A H1N1 virus from their owners. CASE SERIES SUMMARY: Two indoor domestic shorthair cats from the same household were evaluated for acute onset of respiratory distress. The owners had been recovering from flu-like illness at the time of presentation. Venous blood gas showed increased pvCO2 while thoracic radiographs revealed severe bronchointerstitial to alveolar patterns in both cats. The cats were treated with oxygen supplementation, antimicrobials, analgesics, diuretics, corticosteroids, bronchodilators, mechanical ventilation (1 cat), and supportive care. Despite initial improvement in the clinical condition of each cat, respiratory function deteriorated and ultimately both cats were euthanized. Gross and histopathologic examination confirmed diffuse, severe bronchointerstitial pneumonia. Pandemic 2009 influenza A H1N1 viral testing by real time PCR was positive in 1 cat. NEW OR UNIQUE INFORMATION PROVIDED: These cases provide further evidence that domestic felids are susceptible to pandemic 2009 influenza A H1N1 virus, and the literature is briefly reviewed for treatment recommendations. H1N1 should be considered in the differential diagnosis for domestic cats presenting with peracute to acute onset of respiratory distress in the right context. While human-to-cat transmission of H1N1 seems probable in several reported cases, cat-to-human transmission has not been identified.
猫の間質性肺炎interstitial pneumonia または間質性肺疾患interstitial lung disease のPubMed 検索で原因の確定したものをまとめた（ペット家族動物病院西五反田店 近藤絵里子-2019.2.7）。
1）Drolet R. Disseminated tuberculosis caused by Mycobacterium avium in a cat. J Am Vet Med Assoc 1986;189:1336-1337.
A 5-year-old neutered male Siamese cat was examined by a veterinarian because of a recent decrease in appetite and a large lymph node in the left mandibular area. Clinical findings included fever, icterus, leukopenia, and progressive anemia. Despite various treatments, the cat died approximately 3 weeks after initial examination. The main necropsy findings included necrotizing and granulomatous lymphadenitis of the left mandibular lymph node, multifocal necrotizing hepatitis, and interstitial pneumonia. Acid-fast bacilli were detected in lesions of the mandibular lymph node, liver, lung, spleen, and bone marrow. Mycobacterium avium was isolated from the liver. Avian tuberculosis in cats has been reported rarely.
コメント：下顎リンパ節腫大と食欲低下を示した5歳のシャム猫。経過不良で3週間後死亡。剖検にて間質性肺炎を確認した。肝臓からMycobacterium aviumを分離した。猫のMycobacterium avium感染症は報告がまれである（ペット家族動物病院西五反田店 近藤絵里子-2019.2.7）
2）Zhang S, Wilson F, Pace L. Streptococcus pneumoniae-associated cellulitis in a two-month-old Domestic Shorthair kitten. J Vet Diagn Invest 2006;18:221-224.
An approximately 2-month-old, reproductively intact female Domestic Shorthair kitten was presented to the Mississippi Veterinary Research and Diagnostic Laboratory with a history of possible trauma to the left shoulder region while playing with children, and was found dead the following day. Marked swelling, with subcutaneous edema and hemorrhages, was observed in the left forelimb. Severe pleocellular, but largely suppurative cellulitis, fasciitis, and interstitial myositis with edema were observed microscopically in sections from the affected limb. Massive numbers of gram-positive diplococci also were observed. Other pathologic changes included moderate interstitial pneumonia, mild cholangitis, lymph node hemorrhage, gastrointestinal nematodiasis, mild enteritis, and mild interstitial nephritis. Bacteriologic culture identified Streptococcus pneumoniae as the causative agent, which was confirmed by polymerase chain reaction amplification of the pneumolysin gene from chromosomal DNA of the isolate.
3）Bennett AD, Lalor S, Schwarz T, et al. Radiographic findings in cats with mycobacterial infections. J Feline Med Surg 2011;13:718-724.
This study describes radiographic changes associated with mycobacterial infection in 33 domestic cats confirmed by culture or interferon-gamma testing. Infection was seen most frequently in adult (average age 5.7 years; range 1.5-12 years), non-pedigree (87%; 27/31), neutered male cats (69%; 22/32). The most common infections were Mycobacterium microti (60%; 18/30) and Mycobacterium bovis (37%; 11/30); Mycobacterium avium and Mycobacterium malmoense were infrequently cultured (3% of each; 1/30). Radiographs were available for the thorax (24 cats), abdomen (eight), appendicular skeleton (11) and head (three). Radiographic changes affected the thorax most commonly, consisting of bronchial (46%; 11/24), alveolar (38%; 9/24), nodular unstructured interstitial (38%; 9/24) or unstructured interstitial (25%; 6/24) lung patterns, which were often mixed. Perihilar or sternal lymphadenopathy were common (42%; 10/24), particularly perihilar lymphadenopathy (25%; 6/24). Skeletal changes were found in the distal antebrachium (three), pes (two), maxilla, scapula, spine, manus, femur, and tarsus (one each). Changes were typically osteolytic (73%; 8/11), often permeative osteolytic (64%; 7/11). Osteoproliferative changes were seen in three cats and soft tissue swelling in five cats, which were adjacent to the bony abnormality in four cats. Other changes included submandibular soft tissue swelling, marked aortic, aortic root and brachiocephalic trunk calcification, and soft tissue swelling with calcification in the distal antebranchium which was not involving bone. Abdominal changes were uncommon (seen in 2/8 cats) and consisted of hepatomegaly and hepatosplenomegaly. In summary, radiographic changes were varied, no lesion was pathognomic for mycobacterial infection, and pathology was seen most commonly in the thorax.
4）Brooks JW, Roberts EL, Kocher K, et al. Fatal pneumonia caused by Extraintestinal Pathogenic Escherichia coli (ExPEC) in a juvenile cat recovered from an animal hoarding incident. Vet Microbiol 2013;167:704-707.
The current study describes isolation of Extraintestinal Pathogenic Escherichia coli (ExPEC) from a juvenile male cat that died after being rescued from an animal hoarding incident. Grossly, there was evidence of pneumonia and renal abscessation. Histologically, there was diffuse interstitial pneumonia with necrosis and necrotizing and suppurative nephritis with colonies of coccobacilli. Within the lung, kidney, and mesentery there was necrotizing and suppurative vasculitis with thrombosis and coccobacilli. E. coli strain belonging to serotype O6:H1 that carried many of the virulence genes associated with ExPEC was isolated from the lung and kidney. The cat was part of a community of approximately 60 cats that lived in a house in a residential neighborhood, in which multiple cats had died. The case was of major significance to public health, as first responders, animal health professionals, and other community members were likely exposed to ExPEC, which is known to have zoonotic potential. It is important that pet owners, animal health and public health professionals, and first responders be made aware of the potential for zoonotic diseases.
コメント：全身感染。転帰：死亡（ ペット家族動物病院西五反田店 近藤絵里子-2019.2.7）
5）Callegari C, Palermo G, Greco MF, et al. Pneumonia associated with Salmonella spp. infection in a cat receiving cyclosporine. Schweiz Arch Tierheilkd 2014;156:499-503. （PDFあり）
Salmonellosis is uncommon in cats, usually affects the gastrointestinal tract or skin, and can be fatal. This report describes a domestic shorthair cat with severe pneumonia caused by Salmonella spp. without accompanying gastrointestinal or skin manifestations, in which previous administration of cyclosporine may have played a permissive role in its development. Clinical and laboratory findings as well as follow-up are described from diagnosis until complete recovery. This unusual presentation serves to alert practitioners to consider Salmonella spp. as a possible cause of lung disease in cats, especially if immunocompromised.
コメント：重度の肺炎との記述のみで間質性肺炎かどうかは未確認。転帰：完全治癒（ペット家族動物病院西五反田店 近藤絵里子-2019.2.7 ）
6）Major A, Holmes A, Warren-Smith C, et al. Computed tomographic findings in cats with mycobacterial infection. J Feline Med Surg 2016;18:510-517. （PDFあり）
OBJECTIVES: The objective of this study was to describe the CT imaging findings associated with confirmed mycobacterial infection in cats. METHODS: CT images from 20 cats with confirmed mycobacterial disease were retrospectively reviewed. Five cats underwent conscious full-body CT in a VetMouseTrap device. All other cats had thoracic CT performed under general anaesthesia, with the addition of CT investigation of the head/neck, abdomen and limbs in some cases. RESULTS: Mycobacterial infection was seen most frequently in adult (mean age 7.4 years; range 0.6-14 years) neutered male cats (11/20). The most common infections were Mycobacterium microti (6/20) and Mycobacterium bovis (6/20). CT abnormalities were most commonly seen in the thorax, consisting of bronchial (9/20), alveolar (8/20), ground glass (6/20) or structured interstitial (15/20) lung patterns, which were often mixed. Tracheobronchial, sternal and cranial mediastinal lymphadenomegaly were common (16/20). Other abnormalities included abdominal (8/13) or peripheral (10/18) lymphadenomegaly, hepatosplenomegaly (7/13), mixed osteolytic/osteoproliferative skeletal lesions (7/20) and cutaneous or subcutaneous soft tissue masses/nodules (4/20). CONCLUSIONS AND RELEVANCE: CT of feline mycobacteriosis shows a wide range of abnormalities, often involving multiple organ systems and mimicking many other feline diseases. Mycobacteriosis should be considered in the differential diagnosis of thoracic, abdominal and skeletal disorders in cats.
コメント：CTによる評価。骨病変（骨融解・骨増生）あり（ペット家族動物病院西五反田店 近藤絵里子-2019.2.7 ）
7）Cerna P, O’Halloran C, Sjatkovska JO, et al. Outbreak of tuberculosis caused by Mycobacterium bovis in a cattery of Abyssinian cats in Italy. Transbound Emerg Dis 2019;66:250-258. （PDFあり）
Mycobacterium bovis is a re-emerging zoonosis; it was diagnosed in five Abyssinian cats in a breeding cattery in Italy. The infection entered the cattery with an imported kitten (cat A); it had a suspected bite wound on its leg that had been treated at a veterinary clinic in Kiev, Ukraine, which is probably where it became infected with M. bovis. When the kitten arrived in Italy, there were four cats in the cattery; an adult female, her two kittens and a kitten imported from Russia. These were all healthy, and had no outdoor access. All five cats developed tuberculous interstitial pneumonia; in cat A this occurred 6 weeks after importation, the others were diagnosed 4-6 weeks later. Three cats were euthanised with deteriorating pneumonia while two cats remained clinically well on antibiotic therapy (marbofloxacin, doxycycline and azithromycin). The latter cases were euthanised after 5 weeks, as required by Italian law once M. bovis infection was suspected. Changes consistent with tuberculosis on gross post-mortem examination included mesenteric and mediastinal lymphadenopathy, splenomegaly and hepatomegaly, and the presence of disseminated focal white lesions on the cut surface of the spleen, liver and lungs. Visible acid-fast bacteria (cats A, B and C) were confirmed as Mycobacterium tuberculosis complex by PCR (cats A, B, C, D and E), refined to M. bovis (cats A, B and D), spoligotype SB0950 (cats A and D).
コメント：PCRにより確定。咬傷による感染。縦隔、腸間膜リンパ節症あり。3頭安楽死。2頭治癒。治療薬はマルボフロキサシン、ドキシサイクリン、アジスロマイシン（ペット家族動物病院西五反田店 近藤絵里子-2019.2.7 ）
8）Eroksuz Y, Baydar E, Otlu B, et al. Case report: systemic tuberculosis caused by Mycobacterium bovis in a cat. BMC Vet Res 2019;15:9.
BACKGROUND: The diagnosis of previous cases of feline tuberculosis in Turkey has been made based solely on pathological changes without isolation of the causative agent. This case report details the first case of feline tuberculosis in Turkey for which the causative agent (Mycobacterium bovis) was confirmed with microbiological isolation, morphological evaluation, molecular (PCR) characterization and antibiotic sensitivity. CASE PRESENTATION: Systemic tuberculosis was diagnosed via postmortem examination of a 5-year-old stray male cat. Mycobacterium bovis was isolated from the lungs, bronchial and gastrointestinal lymph nodes, kidney and liver. The isolate was defined as M. bovis using the Genotype MTBC assay (Hain Lifescience, Germany), which allows differentiation of species within the Mycobacterium tuberculosis complex with an easy-to-perform reverse hybridization assay. Pathological changes were characterized by multifocal to coalescing granulomatous inflammation in the lungs, liver, lymph nodes and kidneys. Further pathological changes included severe, diffuse, hepatocytic atrophy, periportal fibrosis with lymphohistiocytic infiltration, multifocal lymphohistiocytic interstitial nephritis, mild focal pulmonary anthracosis and mild renal and hepatic amyloidosis. Infection by immunosuppressive viral pathogens including feline herpes virus-1, feline immunodeficiency virus and feline parvovirus virus were ruled out by polymerase chain reaction assay (PCR). The isolated mycobacteria were susceptible to isoniazid, ethambutol, rifampicin or streptomycin. CONCLUSION: Disseminated M. bovis is a rare infection in cats. Involvement of submandibular lymph nodes suggested that primary transmission might have been the oral route in the present case.
コメント：PCRとハイブリダイゼーション法により確定。記述はinterstitial pneumonia ではなくmultifocal to coalescing granulomatous inflammation とある（ペット家族動物病院西五反田店 近藤絵里子-2019.2.7）
9）Kahn DE, Gillespie JH. Feline viruses. X. Characterization of a newly-isolated picornavirus causing interstitial pneumonia and ulcerative stomatitis in the domestic cat. Cornell Vet 1970;60:669-683.
10）Love DN. Feline herpesvirus associated with interstitial pneumonia in a kitten. Vet Rec 1971;89:178-181.
11）Love DN. Pathogenicity of a strain of feline calicivirus for domestic kittens. Aust Vet J 1975;51:541-546. （PDFあり）
12）Hawkins EC, Kennedy-Stoskopf S, Levy JK, et al. Effect of FIV infection on lung inflammatory cell populations recovered by bronchoalveolar lavage. Vet Immunol Immunopathol 1996;51:21-28. （PDFあり）
Human immunodeficiency virus (HIV) and ovine progressive pneumonia virus have been associated with lymphocytic pneumonitis. Pulmonary cell populations in cats infected with feline immunodeficiency virus (FIV) were evaluated by bronchoalveolar lavage (BAL) to identify changes associated with lentivirus infection in this species. Bronchoalveolar lavage was performed through an endotracheal tube using 15 ml kg-1 body weight of sterile 0.9% sodium chloride solution. Results of BAL fluid cytologic analysis from 19 cats experimentally infected with FIV for at least 8 months were compared with results from 34 uninfected cats. Infected cats had significantly higher total cell counts and relative neutrophil counts (P < 0.01). Lymphocytosis did not occur. Bronchoalveolar lavage fluid was collected from nine additional cats prior to, and 2, 6, and 17-18 weeks following infection with FIV. Neither neutrophilia nor lymphocytosis was associated with FIV infection in these cats.
コメント：実験感染。BALF解析による評価。感染後8ヶ月以降は総細胞数の増加、相対的好中球数の増加あり。FIVはリンパ球性肺炎を起こすと言われているが、リンパ球数の増加は認められなかった。また、感染後2、6、17、18週のBALF解析では好中球数、リンパ球数のいずれの増加も認められなかった（2019.2.7 ペット家族動物病院西五反田店 近藤絵里子）
13）Cadore JL, Steiner-Laurent S, Greenland T, et al. Interstitial lung disease in feline immunodeficiency virus (FIV) infected cats. Res Vet Sci 1997;62:287-288. （PDFあり）
Postmortem bronchoalveolar lavage of feline immunodeficiency virus-infected cats indicated an alveolitis process, and histological examination of their lungs confirmed the occurrence of alveolitis, parenchymatous lymphoplasmocytic infiltration and myomatosis. Similar lymphoid interstitial pneumonitis has been described in human and animal lentiviral diseases: lymphocytic interstitial pneumonitis in HIV-1-infected human beings, and maedi in sheep infected by the maedi-visna virus. Such lymphoid interstitial pneumonitis may thus be a common feature of lentiviral infections.
コメント：死後のBALF解析と組織学的な評価により肺胞炎のプロセスを示した。ヒトのHIV-1感染、羊のMaedi-visna virus感染と同様のリンパ球性間質性肺炎がみられ、この像はレンチウイルスに共通の病変と考えられる（ペット家族動物病院西五反田店 近藤絵里子-2019.2.7）。
14）Hooper PT, Westbury HA, Russell GM. The lesions of experimental equine morbillivirus disease in cats and guinea pigs. Vet Pathol 1997;34:323-329. （PDFあり）
Nine cats and four guinea pigs became affected with severe disease during experiments on the infectivity of equine morbillivirus, a newly recognized cause of respiratory disease in horses and humans. Four of the cats were challenged by subcutaneous inoculation, two by intranasal installation, two by oral dosage, and one by direct contact with a cat previously infected by subcutaneous inoculation. All four guinea pigs were inoculated subcutaneously. Gross pathology seen in all affected cats was characterized by hydrothorax and dark, heavy, wet, congested and/or hemorrhagic lungs with froth sometimes found in the respiratory passages. Pulmonary lymph nodes were enlarged and edematous. Six cats also had congested ceca with accompanying edema of mesenteric lymph nodes. Histologically, the lesions in the lungs of the cats were those of severe interstitial pneumonia characterized by serofibrinous alveolar edema, alveolar macrophages, intra-alveolar hemorrhage, thrombosis of small veins, alveolar wall necrosis, and syncytial cells. Clearly defined vascular lesions included intramural hemorrhage, edema, and necrosis and syncytial cells in the endothelium of pulmonary arteries and veins, 20-80 microm in diameter. Vascular lesions accompanied by parenchymal degeneration were also seen in the gastrointestinal and lymphoid organs. Syncytial cells were also visible in the lymphoid tissues of lymph nodes, spleen, and Peyer’s patches. At necropsy, all guinea pigs were cyanosed and had congestion and edema in the gastrointestinal tract. Histologically, there was widespread vascular disease in arteries and veins, 20-80 microm in diameter, in many organs such as the lungs, kidneys, spleens, lymph nodes, gastrointestinal tracts, and skeletal and intercostal muscles, but there was no severe pulmonary edema as seen in horses and cats. Sections of tissues of the cats and guinea pigs, examined by indirect immunocytochemical stains, confirmed that the vascular damage was associated with the presence of equine morbillivirus antigen. The syncytia in small blood vessels in the lungs and other organs of both cats and guinea pigs were similar to those seen in horses, and their presence was interpreted as an important characteristic of the disease consistent with a reaction to a morbillivirus.
15）Campbell RS, Robinson WF. The comparative pathology of the lentiviruses. J Comp Pathol 1998;119:333-395. （PDFあり）
16）Yanai T, Tujioka S, Sakai H, et al. Experimental infection with equine herpesvirus 9 (EHV-9) in cats. J Comp Pathol 2003;128:113-118. （PDFあり）
The pathogenicity for cats of EHV-9, a new neurotropic equine herpesvirus, was assessed by intranasal inoculation with 10(6) plaque-forming units. Four cats killed 4, 5, 6 or 10 days after inoculation showed neurological signs consisting of hyper-excitability and aggressiveness, followed by tremors, occasional convulsions, and depression. Histologically, the cats showed severe encephalitis characterized by neuronal degeneration and loss, intranuclear inclusions, perivascular cuffing and gliosis in the cerebrum. A positive immunohistochemical reaction for EHV-9 antigen was seen in degenerating neuronal cells. The lesions extended from the olfactory bulb to the rhinencephalon and hippocampus. All cats had rhinitis, with or without intranuclear inclusion bodies in the nasal mucosa, and interstitial pneumonia. These findings indicate that the cat, like certain other species such as the goat, is susceptible to experimental infection with EHV-9, and may be at risk from natural infection.
17）German AC, Harbour DA, Helps CR, et al. Is feline foamy virus really apathogenic? Vet Immunol Immunopathol 2008;123:114-118. doi: 10.1016/j.vetimm.2008.01.035.
Feline foamy virus (FFV) is a retrovirus commonly found in cats. It is generally thought to be apathogenic, making it a suitable candidate as a gene therapy vector. However, there have been reports of association of FFV with chronic progressive arthritis and a cofactor effect with feline immunodeficiency virus. This study investigated experimental FFV infection and whether this was associated with signs of disease. Eight young specific pathogen free cats were inoculated intramuscularly with FFV. The cats were examined twice weekly and blood and pharyngeal samples were taken. Haematology, biochemistry and FFV quantitative polymerase chain reaction (qPCR) were performed. Tissue samples were also collected throughout the six month period. FFV was initially detected by qPCR in the blood within the first two weeks of infection and viraemia persisted throughout the study. Two peaks of viraemia were observed, at day 20 (80-170FFU/ml blood) and day 155 (332-415FFU/ml blood). FFV was also consistently detected in oropharyngeal samples after day 36. Anti-FFV IgG was detected in all cats by ELISA; antibody levels had an early peak around day 35 and then increased again following the second rise in circulating viral load. All cats remained clinically normal, except for one cat with an unrelated gingivitis. None of the cats developed pyrexia. The biochemical profile and blood cell counts remained within normal limits except for one cat with a persistent eosinophilia. Initial fluctuations in white cell counts settled within three weeks and did not deviate outside of the normal ranges. All tissue samples contained FFV DNA; lymphoreticular tissues, salivary gland and lung had the highest viral loads. Although there were no gross pathological lesions on post mortem examination, histologically a mild glomerulonephritis and a moderate interstitial pneumonia were observed in all cats. We conclude that during the six month period of infection, although cats appeared clinically normal, histopathological changes were observed in the lungs and kidneys. Further investigation of the significance of these changes is warranted before FFV is developed as a vector for gene delivery.
18）Clinkenbeard KD, Cowell RL, Tyler RD. Disseminated histoplasmosis in cats: 12 cases (1981-1986). J Am Vet Med Assoc 1987;190:1445-1448.
Anemia, weight loss, lethargy, fever, anorexia, and interstitial lung disease were the predominant clinical findings in 12 cats with disseminated histoplasmosis. Some cats were examined because of dysfunction or lesions of bone, eyes, or skin. In most cases, the clinical signs were observed by the owner for 4 weeks or less before seeking veterinary care. Young cats were most commonly affected, with 7 of the 12 cats less than or equal to 1 year old. Identification of Histoplasma organisms in bone marrow aspirates was used to confirm the diagnosis of histoplasmosis in 11 of the 12 cats. Histoplasma infection of multiple organs was found at necropsy. In this study, disseminated histoplasmosis had a higher prevalence in cats than in dogs at the same veterinary medical teaching hospital. Feline disseminated histoplasmosis was not associated with FeLV infection. Treatment was attempted in 7 of the 12 cats.
19）Dubey JP, Lindsay DS, Lipscomb TP. Neosporosis in cats. Vet Pathol 1990;27:335-339. (PDFあり）
Six cats (Nos. 1-6) were inoculated intramuscularly with (1 x 10(6)) and orally (5 x 10(5)) tachyzoites of Neospora caninum. Three (Nos. 1-3) of the six cats were given 40 mg/kg methylprednisolone acetate 7 days before and on the day of inoculation with N. caninum tachyzoites, and three cats (Nos. 4-6) were not given methylprednisolone acetate. Two of the cats (cat Nos. 1 and 2) given methylprednisolone acetate died suddenly. Cat No. 1 died 8 days post-inoculation, and cat No. 2 died 16 days post-inoculation. Cat No. 3 was euthanatized 21 days post-inoculation. Cat No. 1 had lesions of gram-positive bacterial septicemia. Necrotizing encephalitis, myelitis, disseminated skeletal muscle necrosis, hepatic necrosis, interstitial pneumonia, and renal tubular necrosis were the main lesions in cat Nos. 2 and 3. The cats that were not given methylprednisolone acetate remained clinically normal except for slight weight loss in cat No. 6. All three of these cats were euthanatized 55 days post-inoculation. Mild myositis and encephalitis were noted on microscopic examination of tissues from these three cats. Neuromuscular lesions were not seen in six control cats (Nos. 7-12) not inoculated with N. caninum and euthanatized 21 or 22 days after administration of the first two doses of methylprednisolone acetate (40 mg/kg), given at a weekly interval.
20）Eilert D, Hoskinson JJ. What is your diagnosis? Diffuse nodular interstitial-to-alveolar pattern throughout the lungs. J Am Vet Med Assoc 1993;202:456-457.
21）Davidson MG, Rottman JB, English RV, et al. Feline immunodeficiency virus predisposes cats to acute generalized toxoplasmosis. Am J Pathol 1993;143:1486-1497. （PDFあり）
This study was designed to examine the effects of a pre-existing, clinically asymptomatic feline immunodeficiency virus (FIV) infection on a primary challenge with Toxoplasma gondii. Parenteral challenge of FIV-infected cats with tachyzoites of the ME49 strain of T. gondii caused a precipitous drop in all lymphocytes (CD4+, CD8+, and B cells) and generalized severe toxoplasmosis. The predominant postmortem lesions included acute and often fatal interstitial pneumonia, dominated histologically by macrophages, and multifocal to coalescing hepatic necrosis. Immunohistochemistry revealed numerous T. gondii antigen and tachyzoites in macrophages and other cell types in the lung lesions. The proliferative response of peripheral blood mononuclear cells to specific (T. gondii antigen) and nonspecific (Concanavalin A) mitogens was defective in the dually infected cats, suggesting marked immunosuppression. In contrast to the dually infected cats, cats infected only with T. gondii developed a transient, mild clinical disease characterized by anorexia, lethargy, and multifocal chorioretinitis. Lymphocyte changes in T. gondii-infected cats included an early pan-lymphopenia followed by reestablishment of all lymphocyte subset profiles. These cats also showed a reduced proliferative response to Concanavalin A at 1 week after challenge, but a measurable in vivo response to T. gondii antigens, as evidenced by in vitro lymphocyte proliferation in the absence of a mitogenic stimulus. These results show that infection of cats with FIV-NCSU, markedly enhances their susceptibility to a primary T. gondii infection and provides a model to study the mechanisms of the underlying immunological defect(s) occurring early after HIV infection that may predispose individuals to development of acquired immunodeficiency syndrome and associated diseases.
23）Snider TA, Confer AW, Payton ME. Pulmonary histopathology of Cytauxzoon felis infections in the cat. Vet Pathol 2010;47:698-702. （PDFあり）
Cytauxzoonosis, caused by Cytauxzoon felis, is a regionally common, often fatal tick-borne disease primarily affecting the domestic cat. Retrospective analysis of case records from January 1995 to June 2005 identified 148 domestic cats diagnosed with cytauxzoonosis, having suitable archived lung sections. Lung sections were examined and graded on relevant parameters, the chief purpose of which was to characterize the pulmonary lesion of fatal feline cytauxzoonosis. Parameters were scored 0 to 3 for no lesion, mild, moderate, and severe, respectively. Evaluated parameters included the presence of interstitial pneumonia, increases in number of alveolar macrophages, degree of intra-alveolar hemorrhage, neutrophils infiltrating peribronchial and septal interstitium, and degree of vascular occlusion. Overall, interstitial pneumonia was moderate (1.72 +/- 0.65); alveolar macrophage numbers were mild (1.20 +/- 0.60); and intra-alveolar hemorrhage was mild (0.78 +/- 0.75). Neutrophil infiltrates were moderate (1.89 +/- 0.76), and vascular occlusion was moderate to severe (2.26 +/- 0.61). Pulmonary edema was common; its scoring was incorporated into the assessment for interstitial pneumonia. Interestingly, a thrombus was detected in the lung of 1 cat. The current understanding of the pathogenesis of cytauxzoonosis focuses on vascular occlusion by macrophages distended by megaschizont parasite stages within liver, spleen, and lung. These findings corroborate the current understanding yet shed light on the possibility that macrophage activation and inflammatory mediators lead to an interstitial pneumonic process characterized by neutrophilic infiltrates and pulmonary edema. These characterized lesions are likely correlative with the respiratory distress seen in affected cats.
24）Jokelainen P, Simola O, Rantanen E, et al. Feline toxoplasmosis in Finland: cross-sectional epidemiological study and case series study. J Vet Diagn Invest 2012;24:1115-1124.（PDFあり）
Three subgroups of the Finnish cat population underwent investigation for different aspects of feline toxoplasmosis. Blood samples of 445 purebred pet cats and 45 shelter cats were screened for Toxoplasma gondii-specific immunoglobulin G antibodies with a direct agglutination test. The overall seroprevalence was 48.4%; older cats and cats receiving raw meat in their diet were more often seropositive. Fecal samples were obtained from 131 shelters cats; 2 of the cats were found shedding T. gondii-like oocysts, and the oocysts shed by 1 of the 2 were confirmed as T. gondii with polymerase chain reaction. Among 193 cats submitted for necropsy during a 3.5-year period, 6 (3.1%) had been diagnosed with generalized toxoplasmosis and were retrospectively further investigated. The main pathological lesions included acute interstitial pneumonia, acute necrotizing hepatitis, and nonsuppurative meningoencephalitis with glial granulomas. Immunohistochemical staining demonstrated a mild to massive parasite burden in tissues with pathological lesions as well as in unaffected tissues. The results of the direct multilocus genotyping of T. gondii parasites detected were consistent with endemic genotype II, and the causative parasite strains were isolated from 2 of the generalized toxoplasmosis cases. The results indicate that cats in Finland commonly encounter T. gondii and contribute to the environmental oocyst burden, while the endemic genotype II can also prove fatal to the parasite’s definitive host. Preventing feline T. gondii infections is not only of public health importance but also a welfare issue for the cats themselves.
25）Frontera-Acevedo K, Balsone NM, Dugan MA, et al. Systemic immune responses in Cytauxzoon felis-infected domestic cats. Am J Vet Res 2013;74:901-909. （PDFあり）
OBJECTIVE: To characterize systemic immune responses in Cytauxzoon felis-infected cats. SAMPLE: Blood and lung samples obtained from 27 cats. PROCEDURES: Cats were allocated into 4 groups: cats that died of cytauxzoonosis, acutely ill C felis-infected cats, healthy survivors of C felis infection, and healthy uninfected cats. Serum concentrations of tumor necrosis factor-alpha and interleukin-1 beta were measured and serum proteins characterized. Blood smears were stained immunocytochemically and used to assess immunoglobulin deposition. Immunohistochemical expression of CD18 and tumor necrosis factor-alpha were compared in lung tissues obtained from cats that died and healthy uninfected cats. A real-time reverse-transcription PCR assay for CD18 expression was performed on selected blood samples from all groups. RESULTS: Concentrations of both cytokines were greater and serum albumin concentrations were significantly lower in cats that died of cytauxzoonosis, compared with results for all other groups. Erythrocytes from acutely ill cats and survivors of C felis infection had staining for plasmalemmal IgM, whereas erythrocytes from the other groups did not. Increased staining of C felis-infected monocytes and interstitial neutrophils for CD18 was detected. The real-time reverse-transcription PCR assay confirmed a relative increase in CD18 expression in cats that died of cytauxzoonosis and acutely ill cats, compared with expression in other groups. Immunostaining for TNF-alpha in lung samples confirmed a local proinflammatory response. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated immunopathologic responses were greater in cats that died of C felis infection than in cats that survived C felis infection.
26）Nagel SS, Williams JH, Schoeman JP. Fatal disseminated toxoplasmosis in an immunocompetent cat. J S Afr Vet Assoc 2013;84:E1-6.
A 10-year-old domestic short hair cat was referred for investigation of anorexia and polydipsia of 3 days’ duration. Clinically the cat was obese, pyrexic (39.8 degrees C), had acute abdominal pain and severe bilirubinuria. Haematology and serum biochemistry revealed severe panleukopenia, thrombocytopenia, markedly elevated alanine aminotransferase (ALT) and five-fold increased pre-prandial bile acids. Ultrasonographic evaluation of the abdomen did not identify any abnormalities. Serum tests for feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) were negative. Broad-spectrum antibiotic treatment for infectious hepatitis was to no avail; the cat deteriorated and died 72 h after admission. Necropsy revealed mild icterus and anaemia, severe multifocal hepatic necrosis, serofibrinous hydrothorax, pulmonary oedema and interstitial pneumonia. Histopathology confirmed the macroscopic findings and revealed multifocal microgranulomata in the brain and myocardium, as well as areas of necrosis in lymph nodes and multifocally in splenic red pulp. Long bone shaft marrow was hyperplastic with a predominance of leukocyte precursors and megakaryocytes and splenic red pulp showed mild extramedullary haemopoiesis. Immunohistochemical staining for Toxoplasma gondii was strongly positive, with scattered cysts and tachyzoites in the liver, lymph nodes, spleen, lungs, brain, salivary glands and intracellularly in round cells in occasional blood vessels. Immunohistochemical staining for corona virus on the same tissues was negative, ruling out feline infectious peritonitis (FIP). Polymerase chain reaction (PCR) on formalin-fixed paraffin-wax embedded tissues was positive for Toxoplasma sp., but attempts at sequencing were unsuccessful. This was the first case report of fulminant disseminated toxoplasmosis in South Africa, in which detailed histopathology in an apparently immunocompetent cat was described.
コメント：免疫抑制下にない猫の全身性トキソプラズマ症の組織病理。剖検により肺水腫と間質性肺炎の診断。免疫染色とホルマリン材料のPCRよりToxoplasma 陽性を確認。FIV、FeLV、コロナウイルス陰性（ペット家族動物病院西五反田店 近藤絵里子-2019.2.7）。
27）Evans NA, Walker JM, Manchester AC, et al. Acute respiratory distress syndrome and septic shock in a cat with disseminated toxoplasmosis. J Vet Emerg Crit Care (San Antonio) 2017;27:472-478.
OBJECTIVE: To describe acute respiratory distress syndrome (ARDS) and septic shock in a cat with disseminated toxoplasmosis. CASE SUMMARY: A 2-year-old neutered male domestic shorthair cat was presented for acute respiratory distress. At the time of presentation it had been receiving cyclosporine for treatment of eosinophilic dermatitis. Thoracic radiographs revealed severe mixed nodular interstitial and alveolar patterns. An endotracheal wash was performed, which confirmed a diagnosis of pulmonary toxoplasmosis. Despite initial treatment with oxygen supplementation and intravenous clindamycin, the cat developed refractory hypoxemia and hypotension requiring mechanical ventilation and vasopressor support within 24 hours of hospital admission. Cardiac arrest occurred 56 hours after admission. Necropsy was performed and histopathology revealed protozoal organisms disseminated throughout the heart, lungs, liver, and brain. NEW OR UNIQUE INFORMATION PROVIDED: The clinical and necropsy findings presented here are consistent with ARDS secondary to disseminated toxoplasmosis in a cat. This is the first detailed report of ARDS in a cat. Toxoplasma titer testing and antimicrobial prophylaxis should be considered in cats prior to immunosuppressive treatment with cyclosporine.
28）Losonsky JM, Thrall DE, Prestwood AK. Radiographic evaluation of pulmonary abnormalities after Aelurostrongylus abstrusus inoculation in cats. Am J Vet Res 1983;44:478-482.
Bronchial and focal alveolar lung disease was present in cats 3 to 6 weeks after Aelurostrongylus inoculation. More generalized alveolar lung disease was seen during first-stage larval production 5 to 21 weeks after inoculation. Bronchial and interstitial disease entities were seen on radiographs after partial resolution of alveolar disease. These changes were observed 17 to 40 weeks after inoculation.
29）Dillon AR, Tillson DM, Hathcock J, et al. Lung histopathology, radiography, high-resolution computed tomography, and bronchio-alveolar lavage cytology are altered by Toxocara cati infection in cats and is independent of development of adult intestinal parasites. Vet Parasitol 2013;193:413-426. （PDFあり）
This study presents clinical findings after oral ingestion of Toxocara cati eggs which resulted in rapid pulmonary lung migration and parenchymal disease, noted on clinically relevant diagnostic methods. Further, the study investigated the efficacy of pre-infection applications of preventative medication on larval migration through the lungs. A third aim of the study was to determine if adult cats infected with T. cati developed lung disease. Cats in infected groups were administered five oral doses of L3 T. cati larvae. Four-month-old specific pathogen free (SPF) kittens were divided into three groups (six per group): an infected untreated group, an uninfected untreated control group, and an infected treated group (topical moxidectin and imidacloprid, Advantage Multi for Cats, Bayer Healthcare LLC). Six 2- to 3-year-old adult multiparous female SPF cats were an infected untreated adult group. The cats were evaluated by serial CBCs, bronchial-alveolar lavage (BAL), fecal examinations, thoracic radiographs, and thoracic computed tomography (CT) scans and were euthanized 65 days after the initial infection. Adult T. cati were recovered in infected untreated kittens (5/6) and infected untreated adults (5/6) in numbers consistent with natural infections. Eggs were identified in the feces of most but not all cats with adult worm infections. No adult worms were identified in the uninfected controls or the infected treated group. All cats in the infected groups, including treated cats and untreated cats without adult worms, had lung pathology based on evaluation of radiography, CT scans, and histopathology. The infected cats demonstrated a transient peripheral eosinophilia and marked eosinophilic BAL cytology, but normal bronchial reactivity based on in vivo CT and in vitro ring studies. Lung lesions initially identified by CT on day 11 were progressive. Thoracic radiographs in infected cats had a diffuse bronchial-interstitial pattern and enlarged pulmonary arteries. Pulmonary arterial, bronchial, and interstitial disease were prominent histological findings. Infected treated cats had a subtle attenuation but not prevention of lung disease compared to infected cats. Significant lung disease in kittens and adult cats is associated with the early arrival of T. cati larvae in the lungs and is independent of the development of adult worms in the intestine. These data suggest that while the medical prevention of the development of adult parasites after oral exposure to T. cati is obviously beneficial, this practice even with good client compliance will not prevent the development of lung disease which can alter clinical diagnostic methods.
コメント：SPF子猫および成猫に対する実験感染。肺の検索は胸部X線、CT、病理組織による。胸部X線検査所見はびまん性の気管支−間質パターンと肺動脈の拡張であった。肺の組織像は動脈、気管支、間質に明らかな病変があり、これは治療群では軽度に抑えられているものの完全に抑制されてはいなかった。T. cati 幼虫が肺に到達する際に起こす初期病変は腸管における成虫寄生の進行とは無関係に起こる。これらのデータが示すのは駆虫は明らかに効果的だが、肺における病変の進行を防止するに至らないということである（ペット家族動物病院西五反田店 近藤絵里子-2019.2.7）。
30）Dennler M, Bass DA, Gutierrez-Crespo B, et al. Thoracic computed tomography, angiographic computed tomography, and pathology findings in six cats experimentally infected with Aelurostrongylus abstrusus. Vet Radiol Ultrasound 2013;54:459-469. （FDFあり）
Aelurostrongylus abstrusus infection is common in endemic areas and may cause severe respiratory clinical signs. Computed tomography (CT) is an important tool to diagnose pulmonary disease, because it allows detection of small lesions and discrimination of superimposed structures. The purpose of this study was to characterize by CT and angiographic CT the pulmonary lesions in six cats before, and 48 and 81 days after inoculation with 100 or 800 A. abstrusus infective larvae. Histological examination of the accessory lung lobe was performed to determine the microscopic, pathomorphologic correlate of the CT findings. The predominant CT lesion consisted of multiple nodules of varying size distributed throughout the lungs, severity depending on infectious dose. The histological correlate of the nodular lesions was multifocal dense granulomatous to mixed inflammatory cell infiltrates, including eosinophils distributed in the parenchyma and obliterating the alveoli. Marked, multifocal, dose-dependent thickening of the bronchi and adjacent interstitial changes blurred the margins of the outer serosal surface of the bronchi and vessels. Histologically, this was due to peribronchial mixed cell inflammation. During the course of infection some of the nodular and peribronchial changes were replaced by areas of ground-glass opacity. In addition to providing detailed depiction of pulmonary lesions resulting from an infectious cause and clearly defining lesions with respect to time and severity of infection, CT allowed quantitative assessment of bronchial thickness and lymph node size during the course of disease. Findings indicated that CT characteristics of this disease are consistent with pathologic findings.
31）Philbey AW, Krause S, Jefferies R. Verminous pneumonia and enteritis due to hyperinfection with Aelurostrongylus abstrusus in a kitten. J Comp Pathol 2014;150:357-360. （PDFあり）
Severe infestation with Aelurostrongylus abstrusus was identified in the lungs and small intestine of a 2-month-old kitten that died due to verminous pneumonia and enteritis. On clinical examination, the kitten had dyspnoea, pneumonia, pleural effusion, ascites and diarrhoea. An interstitial pattern was evident radiographically in the lungs. The kitten died before treatment could be instituted. On gross and histopathological examination, there was severe interstitial pneumonia and large numbers of A. abstrusus eggs and larvae were present in alveoli, together with fewer adult nematodes in small bronchioles. The mucosa of the small intestine was invaded by large numbers of A. abstrusus larvae. The findings were consistent with a hyperinfection syndrome due to A. abstrusus.
32）Brianti E, Gaglio G, Napoli E, et al. Feline lungworm Oslerus rostratus (Strongylida: Filaridae) in Italy: first case report and histopathological findings. Parasitol Res 2014;113:3853-3857.
Oslerus rostratus syn. Anafilaroides rostratus (Strongylida: Filaroididae) is a metastrongyloid transmitted by snails, which localizes in peri-bronchial tissues and in the lung parenchyma of wild as well as domestic cats. In Europe, this nematode has been reported only on two occasions, being diagnosed in cats from Majorca Island and in northern Spain. Here, we describe a case of O. rostratus infection in a necropsied 4-year-old cat in Sicily (southern Italy). At the inspection of lungs, slender and greyish nematodes (four females and two males) were found embedded in the peri-bronchial tissues and in the bronchial walls. Parasites were morphological and molecularly identified as O. rostratus, with their 18S sequences being identical among them and showing a high homology (99%) with those available in public databases. At the histology, nematodes were encapsulated in a pseudo-cystic formation surrounded by an interstitial inflammatory process and fibrous tissue. Lung lesions were mainly represented by peri-luminal fibrosis, hyperplasia and hypertrophy of the bronchial mucosa and glands, respectively. This first record of O. rostratus infection from Italy indicates that this parasite should be included in the differential diagnosis of feline of lungworm infection.
33）Ray Dillon A, Tillson DM, Wooldridge A, et al. Effect of pre-cardiac and adult stages of Dirofilaria immitis in pulmonary disease of cats: CBC, bronchial lavage cytology, serology, radiographs, CT images, bronchial reactivity, and histopathology. Vet Parasitol 2014;206:24-37. （PDFあり）
A controlled, blind study was conducted to define the initial inflammatory response and lung damage associated with the death of precardiac stages of Dirofilaria immitis in cats as compared to adult heartworm infections and normal cats. Three groups of six cats each were used: UU: uninfected untreated controls; PreS I: infected with 100 D. immitis L3 by subcutaneous injection and treated topically with selamectin 32 and 2 days pre-infection and once monthly for 8 months); IU: infected with 100 D. immitis L3 and left untreated. Peripheral blood, serum, bronchial lavage, and thoracic radiographic images were collected from all cats on Days 0, 70, 110, 168, and 240. CT images were acquired on Days 0, 110, and 240. Cats were euthanized, and necropsies were conducted on Day 240 to determine the presence of heartworms. Bronchial rings were collected for in vitro reactivity. Lung, heart, brain, kidney, and liver tissues were collected for histopathology. Results were compared for changes within each group. Pearson and Spearman correlations were performed for association between histologic, radiographic, serologic, hematologic and bronchoalveolar lavage (BAL) results. Infected cats treated with selamectin did not develop radiographically evident changes throughout the study, were heartworm antibody negative, and were free of adult heartworms and worm fragments at necropsy. Histologic lung scores and CT analysis were not significantly different between PreS I cats and UU controls. Subtle alveolar myofibrosis was noted in isolated areas of several PreS I cats and an eosinophilic BAL cytology was noted on Days 75 and 120. Bronchial ring reactivity was blunted in IU cats but was normal in PreS I and UU cats. The IU cats became antibody positive, and five cats developed adult heartworms. All cats with heartworms were antigen positive at one time point; but one cat was antibody positive, antigen negative, with viable adult females at necropsy. The CT revealed early involvement of all pulmonary arteries and a random pattern of parenchymal disease with severe lesions immediately adjacent to normal areas. Analysis of CT 3D reconstruction and Hounsfield units demonstrated lung disease consistent with restrictive pulmonary fibrosis with an interstitial infiltrate, absence of air trapping, and decrease in total lung volume in Group IU as compared to Groups UU and PreS I. The clinical implications of this study are that cats pretreated with selamectin 1 month before D. immitis L3 infection did not become serologically positive and did not develop pulmonary arterial hypertrophy and myofibrosis.
34）Gambino J, Hiebert E, Johnson M, et al. Diagnosis of Aelurostrongylus abstrusus verminous pneumonia via sonography-guided fine-needle pulmonary parenchymal aspiration in a cat. JFMS Open Rep 2016;2:2055116916646584. （PDFあり）
Case summary A 9-year-old, male neutered, indoor-outdoor domestic shorthair cat from the northern Alabama countryside presented for a 3 week history of coughing, lethargy and an episode of self-resolving dyspnea that occurred 1 week prior to presentation. Three-view thoracic radiographs revealed a moderate-to-severe, diffuse, mixed bronchial to structured interstitial (miliary-to-nodular) pulmonary pattern in all lung lobes with peribronchial cuffing and multifocal areas of mild patchy alveolar opacity. Ultrasound-guided evaluation and fine-needle aspiration of the caudodorsal lung parenchyma was performed with sedation. Cytology revealed many widely scattered Aelurostrongylus abstrusus larvae and ova. Upon the confirmed diagnosis of A abstrusus verminous pneumonia, treatment with fenbendazole and selamectin resulted in complete resolution of clinical signs within 6 weeks of the initial diagnosis. Relevance and novel information We report herein the first documented case in the Americas of A abstrusus verminous pneumonia diagnosed via cytologic evaluation of an in vivo, percutaneous ultrasound-guided fine-needle aspirate of affected lung. Additionally, to our knowledge, we offer the first account of the sonographic (pulmonary) features of the disease.
コメント：猫肺虫症。鎮静下、エコーガイド下FNAにより確定診断。胸部X線所見はびまん性気管支−網状間質影（多発粒状/結節影）が全肺野にわたって認められ、気管支周囲浸潤影、多巣性斑状の肺胞浸潤影、軽度を伴う。A. abstrusus による肺病変のエコー像を示した最初の報告である。転帰：治癒（ペット家族動物病院西五反田店 近藤絵里子-2019.2.7）。
35）Lacava G, Zini E, Marchesotti F, et al. Computed tomography, radiology and echocardiography in cats naturally infected with Aelurostrongylus abstrusus. J Feline Med Surg 2017;19:446-453.
Objectives The aims of the study were to describe the radiographic and computed tomographic features in cats naturally infected with Aelurostrongylus abstrusus, and to identify signs of pulmonary hypertension with echocardiography. Methods Fourteen cats positive on Baermann test for A abstrusus were included in the study. All cats underwent thoracic radiography, CT and echocardiography. Results The most common clinical signs were coughing (10/14) and dyspnoea (5/14). Radiographic findings included a generalised unstructured interstitial pulmonary pattern (8/14), mixed bronchointerstitioalveolar pattern (3/14) and bronchointerstitial pattern with bronchial wall thickening (3/14). Sternal lymphadenopathy was detected on thoracic radiographs in six cats. On CT, features were mixed bronchointerstitioalveolar pattern with ground-glass appearance in six cats, interstitioalveolar with multiple pulmonary nodules in five, interstitial ground-glass infiltrates in three, regional lymph node enlargement in 11 (10 sternal, three cranial mediastinal and three tracheobronchial lymph nodes) and subpleural thickening in four. None of the thoracic radiographs revealed subpleural thickening. In all cases, pulmonary vessels were normal in terms of size, shape and attenuation on both radiography and CT. Pulmonary hypertension and cardiac abnormalities were not observed in any cat during echocardiography. Conclusions and relevance CT provided a more thorough characterisation of pulmonary and mediastinal lesions compared with thoracic radiographs in cats naturally infected with A abstrusus. Although feline aelurostrongylosis has been previously associated with histopathological lesions in lung arteries, in this cohort clinical evidence of pulmonary hypertension was not documented.
36）Crisi PE, Aste G, Traversa D, et al. Single and mixed feline lungworm infections: clinical, radiographic and therapeutic features of 26 cases (2013-2015). J Feline Med Surg 2017;19:1017-1029. （PDFあり）
Objectives The aim of this study was to retrospectively describe clinical, radiographic and therapeutic features of feline lungworm infection. Methods Medical records of cats with lungworm diagnosis, thoracic radiography and without concurrent diseases between 2013 and 2015 were reviewed. Collection of data included physical examination, haematology, serum biochemistry, therapy with a variety of anthelmintics and outcomes. Results Thirty-seven records were recovered and 26 were included in the study. Single infections by Aelurostrongylus abstrusus (n = 15), Troglostrongylus brevior (n = 3) and Capillaria aerophila (n = 1) and coinfections by T brevior/ A abstrusus (n = 6) and T brevior/ C aerophila (n = 1) were diagnosed. The most common respiratory signs were coughing (n = 12), increased vesicular sounds (n = 10), dyspnoea (n = 9), such as laboured breathing, orthopnoea or open-mouth breathing, and tachypnoea (n = 6). Two cats were subclinically infected. The most common laboratory abnormality was anaemia (n = 7). Radiographic patterns recorded were interstitial (n = 24), bronchial (n = 21), alveolar (n = 10) and vascular (n = 2). Twenty-five cats had a complete recovery within 2-6 weeks of therapy. One kitten died 7 days after the diagnosis. Conclusions and relevance Lungworms should always be included in the differential diagnosis in cats living in endemic areas and presenting with respiratory signs and radiographic abnormalities. A copromicroscopic examination should be considered as the first diagnostic step for all cats at risk of lungworm infections. In most cases, timely therapy with a variety of anthelmintics guarantees recovery.
コメント：肺虫症（Aelurostrongylus abstrusus、Troglostrongylus brevior、Capillaries aerophila）の単独または混合感染例の報告。最も一般的な呼吸器症状は咳（12/26）、コースクラックル（10/26）、呼吸困難（9/26）、頻呼吸（6/26）。胸部X線所見は間質影（24/26）、気管支影、（21/26）浸潤影（10/26）、血管影（2/26）。転機：治癒（25/26）死亡（1/26＝子猫）（ペット家族動物病院西五反田店 近藤絵里子-2019.2.7）。
37）Panopoulos I, Specchi S, Soubasis N, et al. Multidetector computed tomographic pulmonary angiography in a cat with fatal heartworm disease. Vet Radiol Ultrasound 2018;59:E71-E75. （PDFあり）
A 17-month-old neutered male domestic shorthair cat was referred for a computed tomographic (CT) study of the thorax due to respiratory distress. Multidetector CT angiography showed a multifocal interstitial ground glass opacity, tortuous and blunted pulmonary arteries consistent with thromboembolism with perivascular lung infiltration and hypoventilation in multiple lung lobes. A blood antigen test was positive for Dirofilaria immitis. The cat’s clinical condition rapidly declined and the owners elected euthanasia. The histopathologic examination confirmed heartworm disease with parasitic pulmonary thromboembolism.
コメント：7歳ドメスティックショートヘア猫のDilofilaria immitis自然感染例。症状は呼吸困難。CT所見は多巣性間質性すりガラス影、肺塞栓を表す肺動脈の蛇行ならびに切り詰め像、複数の肺葉における血管周囲浸潤と肺胞虚脱を伴う。転帰：安楽死（ペット家族動物病院西五反田店 近藤絵里子-2019.2.7）。
38）Forrest LJ, Graybush CA. Radiographic patterns of pulmonary metastasis in 25 cats. Vet Radiol Ultrasound 1998;39:4-8. （PDFあり）
Thoracic radiographs of 25 cats with pulmonary metastatic disease and confirmed primary tumors were reviewed retrospectively. Pulmonary patterns of metastasis were divided into three categories, described as well-defined interstitial nodules, ill-defined interstitial nodules or a diffuse pulmonary pattern. The latter consisted of an alveolar pattern with or without ill-defined pulmonary nodules and/or pleural effusion. More cats presented with pulmonary metastatic disease in the category of either ill-defined nodules (n = 10) or a diffuse pattern (n = 7). Within this group, the most commonly represented primary tumor was mammary gland adenocarcinoma.
39）Geyer NE, Reichle JK, Valdes-Martinez A, et al. Radiographic appearance of confirmed pulmonary lymphoma in cats and dogs. Vet Radiol Ultrasound 2010;51:386-390.
Herein we describe the thoracic radiographic appearance of confirmed pulmonary lymphoma. Patients with thoracic radiographs and cytologically or histologically confirmed pulmonary lymphoma were sought by contacting American College of Veterinary Radiology members. Seven cats and 16 dogs met the inclusion criteria, ranging in age from 4 to 15 years. Method of diagnosis was via ultrasound-guided cytology (four), surgical biopsy (two), ultrasound-guided biopsy (one), and necropsy (16). Radiographic findings varied but ranged from normal (one) to alveolar (six) and/or unstructured interstitial infiltrates (11), nodules and/or masses (eight), and bronchial infiltrates (four). Additional thoracic radiographic findings included pleural effusion and lymphadenopathy. The results of this evaluation indicate a wide variability in thoracic radiographic abnormalities in cats and dogs with pulmonary lymphoma.
40）Romanucci M, Massimini M, Aste G, et al. Diffuse Pulmonary Adenocarcinoma with Micropapillary Growth Pattern in a Cat. J Comp Pathol 2018;160:34-38. （PDFあり）
A 12-year-old female European shorthair cat was presented with severe dyspnoea. Echocardiography revealed hypertrophic cardiomyopathy and pleural effusion. The cat died from acute decompensated left heart failure. At necropsy examination, the lungs were diffusely congested and firm, with multifocal grey areas and sparse haemorrhages. No solid masses were detected. Histopathology revealed a diffuse neoplastic proliferation characterized by irregular growth along alveolar walls with a micropapillary pattern. Tumour cells were large, highly pleomorphic and intensely positive for pan-cytokeratin and CAM 5.2. Tumour growth was obscured by simultaneous lesions related to chronic pulmonary congestion and interstitial lung disease. Histological features were consistent with a diffuse invasive pulmonary adenocarcinoma with a micropapillary pattern of tumour growth. Differential diagnosis included large cell carcinoma, which is usually characterized by rosettes or solid clusters of cells occupying alveolar lumen. Extensive cytokeratin immunolabelling was helpful in the differentiation from histiocytic proliferative disease.
41）Horsky P. [Pulmonary damage following assisted ventilation and oxygenotherapy in the cat (author’s transl)]. Respiration 1977;34:278-284.
Groups of 6 cats were curarized and maintained under assisted ventilation with either air or a 35% oxygen mixture. Lungs were then fixed and divided in small pieces, some of which were chosen at random for histological studies. Pulmonary lesions after assisted ventilation with air were rather discrete, even after 72 h. On the contrary, after the same period of ventilation with 35% O2, all cats showed capillary dilatation, interstitial edema and intra-alveolar hemorrhagic exsudate.
42）Plopper CG, Hyde DM, Weir AJ. Centriacinar alterations in lungs of cats chronically exposed to diesel exhaust. Lab Invest 1983;49:391-399.
This study describes the morphologic changes in the centriacinar regions of lungs following long-term exposure of cats to diesel exhaust. Nine male cats (13 months of age) from a minimal disease colony were exposed to diesel exhaust for 8 hours/day, 7 days/week for 27 months. Eight cats were exposed to filtered air. Following exposure, the animals were killed by exsanguination and the lungs and trachea removed from the chest by thoracotomy, weighed, and fixed via tracheal cannula with glutaraldehyde/paraformaldehyde (550 mOsmoles, pH 7.4) at 30 cm of pressure. Centriacinar regions were selected from fixed tissue, the airways bisected, and complementary tissue halves processed by a large block method for high resolution light microscopy and for scanning electron microscopy. Compared with controls, diesel-exposed cats had lower fresh lung and kidney weights and lower fixed volumes of the right cranial lobe. The volume fractions of pulmonary parenchyma and nonparenchyma were unchanged. Epithelium of terminal and respiratory bronchioles in exposed cats consisted of three types of cells (ciliated, basal, and Clara cells), compared with only one type (Clara cells) in controls. Carbon-laden macrophages were found filling alveolar and interstitial spaces in exposed animals. Type 2 pneumocyte hyperplasia was present in proximal interalveolar septa. More distal alveolar ducts and the majority of the rest of the parenchyma were unchanged from controls. We concluded that exposure to diesel exhaust produces changes in both epithelial and interstitial tissue compartments and that the focus of these lesions in peripheral lung is the centriacinar region where alveolar ducts join terminal conducting airways.
43）DiBartola SP, Tarr MJ, Benson MD. Tissue distribution of amyloid deposits in Abyssinian cats with familial amyloidosis. J Comp Pathol 1986;96:387-398. （PDFあり）
The tissue distribution of amyloid deposits was studied in 15 related Abyssinian cats with familial amyloidosis. There was interstitial medullary amyloidosis in the kidneys of all 15 cats but only 11 had detectable glomerular involvement. The thyroid glands, stomach and colon were affected in all cats examined. Most of the cats also had amyloid deposits in the small intestine, spleen, heart, adrenals, pancreas, liver, lymph nodes and bladder. In 50 per cent or fewer of the cats examined, there was involvement of the parathyroids, lung and gonads. The central nervous system was not involved in any of the 3 cats evaluated. In 8 of the cats, no concurrent inflammatory disease could be detected. The tissue distribution of amyloid deposits resembled that found in other breeds of domestic cats with systemic amyloidosis. Despite the wide tissue distribution of amyloid deposits, clinical signs were related to renal amyloidosis. Familial amyloidosis in the Abyssinian cat may represent a valuable spontaneous animal model for the study of Familial Mediterranean Fever in man and the pathogenesis of reactive amyloidosis in general.
44）Stalis IH, Bossbaly MJ, Van Winkle TJ. Feline endomyocarditis and left ventricular endocardial fibrosis. Vet Pathol 1995;32:122-126. （PDFあり）
A retrospective study was conducted of all feline necropsies over a 7-year period. Of a total of 1,472 necropsies, 37 cases of endomyocarditis (EMC) and 25 cases of left ventricular endocardial fibrosis (LVEF) (previously called restrictive or intermediate cardiomyopathy) were identified. There was a subset of four cats with EMC that had histologic features of both diseases. Interstitial pneumonia was seen in 25 of 35 cats (71%) with EMC but in only seven of 25 cats (28%) with LVEF. Thrombi or thromboemboli were seen in 14 of 25 cats (56%) with LVEF but in only six of 37 of cats (16%) with EMC. In both LVEF and EMC, thromboemboli were located in the abdominal aorta, left atrium and ventricle of the heart, femoral artery, cranial mesenteric artery, liver, pulmonary artery, jugular vein, or a meningeal vessel. Each cat had a single thrombus/thromboembolus, except for four cats with LVEF that had more than one. The histologic and clinical findings suggest that EMC and LVEF represent temporally different manifestations of a single disease entity.
Extraintestinal pathogenic E. Coli4）
Feline immunodificiency virus (Lenti virus)12）＊13）15）
Equine herpesvirus 916）＊
Feline foamy virus17）
Reinero C. Interstitial lung diseases in dogs and cats part I: The idiopathic interstitial pneumonias. Vet J 2019;243:48-54. （PDFあり）
Interstitial lung diseases (ILDs), also called diffuse parenchymal lung diseases, are a large heterogenous group of non-infectious, non-neoplastic disorders characterized by varied patterns of inflammation and fibrosis (Travis et al., 2002). In humans, accurate classification of interstitial lung diseases (ILDs) requires multidisciplinary collaboration between clinicians, radiologists and pathologists. The same is likely to be true for canine and feline ILDs; however, this collaborative approach is rarely taken, leading to a paucity of knowledge of ILDs in small animal species. A proposed classification scheme of canine and feline ILDs, modified from a human classification scheme, consists of three major groups: idiopathic interstitial pneumonias (IIPs), ILDs secondary to known causes, and miscellaneous ILDs (Travis et al., 2002). The focus of this review is on the IIPs in dogs and cats. A framework of what is known about the major IIPs in humans will be used to draw parallels when relevant to the canine and feline species. Differences will also be highlighted. When available from the veterinary literature, clinical presentation, diagnostic results, treatment and/or prognosis will be reported. The review underscores that to advance in our knowledge of veterinary IIPs and other ILDs, clinicopathologic features, advanced imaging and histopathology must be carefully integrated and larger groups of animals studied.
コメント：特に線維性間質性肺炎について-犬と猫では線維性間質性肺炎は肺線維症として単一の「病気」と認識されているが、そうではなく、さまざまな損傷の最終段階を表すと考えられる。肺生検では最も目に見える重度の病変のみをサンプリングすると重度の病変は末期線維症を確認するかもしれないが、そこに至るまでの初期の段階での領域を取り損じることにより治療可能な根本的な過程を見逃すかもしれないため複数箇所の生検が必要となる。 より早い認識と評価が不可逆的な変化が起こる前に介入する機会与えてくれるかもしれない。 （代官山動物病院 明石依里子-2019.3.14）
Reinero C. Interstitial lung diseases in dogs and cats part II: Known cause and other discrete forms. Vet J 2019;243:55-64. （PDFあり）
In addition to idiopathic interstitial pneumonias, interstitial lung diseases (ILDs) can occur secondary to known causes or be classified as discrete syndromes. Also known as diffuse parenchymal lung diseases, the ILDs represent a heterogenous group of non-infectious, non-neoplastic disorders characterized by varied patterns of inflammation and fibrosis. Characteristically associated with the true interstitium (i.e. the anatomic space lined by alveolar epithelial cells and capillary endothelial cells and the loose-binding connective tissue), it is important to understand ILDs are associated with pathology of the distal lung parenchyma and thus lesions can be bronchiolocentric or resemble alveolar filling disorders. Injury to the distal lung can occur via inhalation or hematogenous routes. This review will build on a proposed classification scheme adapted from human medicine to describe known cause and discrete forms of ILDs in dogs and cats.
コメント：犬や猫の間質性肺疾患に関する知識はまだ初期の段階である。改良された画像診断ツール、特に胸部CTは、間質性肺疾患の認識を高め、治療の介入が予後により良い影響を与えうる疾患に対して、早い段階での肺生検の理論的根拠を提供するかもしれない。 臨床医、放射線科医および病理学者の間の協力が、この分野を発展させるための鍵となる（代官山動物病院 明石依里子-2019.3.14）。
城下幸仁, 稲葉健一. 猫の気管支ろう18例. 第38回動物臨床医学会年次大会プロシーディングno.3 2017:37-41.
Y. Shiroshita KI, Y. Akashi, H. Nakano, K. Yamashita, T. Taniguchi, E. Kondo. Feline Bronchorrhea: A Retrospective Study of 18 Cases (2012-2017). ACVIM 2019, Phenix, AZ.
Chronic pulmonary disease in cats that exhibit rattling sounds and airway hypersecretion through bronchoscopy is often experienced in respiratory clinic, however clinical information of this disease is limited. This feline disease is comparable to human bronchorrhea. This study aimed to describe clinical features of feline bronchorrhea. Medical records of 18 cats with over 1-month episodes of intermittent rattling, moist cough, respiratory efforts, pulmonary infiltrates or interstitial pattern on chest X-ray, and airway hypersecretion diagnosed with bronchoscopy between 2012 and 2017 were reviewed. Survival time and quality of life during the follow-up period (good/fair/poor) among therapies were compared using the chi-square test. A P-value < 0.05 was considered statistically significant.
In this study, Russian blue (7/18) and American Shorthair (5/18) cats were predisposed. The median age was 8.5 (6–13) years. In addition, rattling on admission (11/18), infrequent moist cough (3–10 events/day, 8/18), rapid and labored breathing (13/18), increased breath sounds on chest auscultation (12/18), mild hypoxemia (mean arterial partial pressure of oxygen: 69.5 mmHg) were representative. Chest X-ray densities were predominant on the right posterior lung fields (11/18), including diffuse patchy pulmonary infiltrates (6/18), pulmonary hyperinflation (7/18), and broncholithiasis (4/18). Three of six cats that were undergone chest computed tomography (CT) revealed consolidation within multiple cysts (< 3.0 cm in diameter). One cat revealed an enlargement of thoracic lymph nodes on CT and died 2 days after the diagnosis. In all cats, bronchoscopy revealed marked airway secretion (watery: 16; thick: 2). Transbronchial lung biopsy samples in eight cats were malignant in two and benign in six. Bronchoalveolar fluid cytology in nine cats revealed mainly foamy macrophages (median: 67.5%), with elevated neutrophils (median: 22.3%). Bacterial cultures in airway samples were negative in 16, insignificant in 2, and positive in none of the cats. Lobectomies including the primary lesions in five selected cats revealed interstitial pneumonia in two, bronchioloalveolar carcinoma in two, and adenocarcinoma in one. The 60-day survival rate was 72.2%. The median survival time (MST) was 374 days in 16 cats that were prescribed feasible combined therapies, whereas 9 days in 2 cats prescribed no therapy. The MST in cats (n = 5) received lobectomy was significantly longer than that in cats (n = 13) not received lobectomy（596 vs. 222 days; P < 0.05). Furthermore, “Age on admission < 10 years” and “no enlargement of thoracic lymph node on CT” significantly correlated with good or fair QOL (P < 0.05).
Feline bronchorrhea has distinguishing clinical characteristics with relatively poor prognosis. Early identification, initiation of even one feasible therapy, and, if possible, lobectomy could enhance the prognosis. The pathology and etiology of the disease needs to be explored concurrently.
Marom ZM, Goswami SK. Respiratory mucus hypersecretion (bronchorrhea): a case discussion–possible mechanisms(s) and treatment. J Allergy Clin Immunol 1991;87:1050-1055. https://www.jacionline.org/article/0091-6749(91)92149-U/pdf
The mechanism(s) underlying mucus hypersecretion (bronchorrhea) and the treatment of this condition are poorly understood. We have previously demonstrated that erythromycin inhibited mucus secretion from human airways and from secretory epithelial cells in vitro. We encountered a patient with airway obstruction marked by severe bronchorrhea, who previously had responded only to inhaled bronchodilators and high-dose prednisone. Many attempts to wean him from prednisone had failed. During the course of his disease, he had developed an IgG antibody to vasoactive intestinal peptide, had increased amounts of mucus secreted by his respiratory epithelial cells, and demonstrated hyperreactive airways as measured by methacholine challenge provocation test. Erythromycin was added to his therapy. The effect of erythromycin treatment was quite dramatic and included clinical and laboratory improvement. After a short trial of erythromycin, the patient tolerated low, every-other-day doses of prednisone. there was a significant reduction in the volume of his bronchorrhea, a major decrease in the epithelial mucins in his total expectorated mucus, complete inhibition of his airway hyperresponsiveness to inhaled methacholine, and significant reduction in the level of IgG antibody to vasoactive intestinal peptide. This response was specific for erythromycin since other antibiotics did not have any clinical, biochemical, or physiologic effects. We conclude that erythromycin may play a role in the treatment of patients with bronchorrhea and may have a steroid-sparing effect. Additional studies with larger numbers of patients are indicated.
エリスロマイシンは1）直接の粘液分泌抑制効果、2）マクロファージに働きかけ、マクロファージ由来分泌促進物質の産生を抑制する効果の２つを持つと考えられている（ペット家族動物病院西五反田店 近藤絵里子-2019.3.12 ）。
Shimura S, Sasaki T, Sasaki H, et al. Chemical properties of bronchorrhea sputum in bronchial asthma. Chest 1988;94:1211-1215.
Bronchorrhea, defined as watery sputum of 100 ml or more per day, was seen in 18 of 207 patients (8.7 percent) with bronchial asthma during attack. Fifteen bronchorrhea sputum samples were chemically examined using ten parameters: dry weight, albumin, IgA, pH, Na+, Cl-, K+, prostaglandins E and F and histamine, and compared with eight saliva samples and 17 mucoid sputum samples. Bronchorrhea sputum differed from saliva in its chemical parameters. Bronchorrhea sputum exhibited parameter values intermediate between those of saliva and mucoid sputum, except for the two following parameters. The pH of bronchorrhea sputum was significantly lower than that of mucoid sputum and histamine concentration, expressed as weight per dry weight of sample, was significantly higher in bronchorrhea than in mucoid sputum. Administration of corticosteroid or an histamine H1-blocker to five to nine asthmatic patients with associated bronchorrhea sputum during asthmatic attacks, significantly reduced the volume of bronchorrhea sputum, whereas anticholinergics and H2-blocker did not alter the sputum volume.
Sung CY, Lee TH, Chu NS. Bronchorrhea following Stroke. Eur Neurol 2012;67:57-62.
BACKGROUND: Stroke-induced excessive bronchial secretion is not rare, but seldom discussed. This study emphasizes its recognition, pathophysiology and treatment. METHODS: We prospectively collected data from 19 consecutive stroke patients with bronchorrhea who were admitted within 2 days of stroke onset. RESULTS: Sixteen of them (84%) suffered from ischemic stroke, and 3 patients (16%) had hemorrhage. All of them had brainstem involvement, and 11 of them (58%) had localized lesions in the dorsal lateral medulla. In 15 patients (79%), copious secretion developed within 3 days after stroke onset. The frequency of expectoration was variable with fluctuation, and half of the patients (47%) had to spit every 2-5 min during its climax. The duration of increased secretion ranged from 4 days to over 2 months. Half of the patients (53%) received anticholinergic treatment, and the response was fair to good. CONCLUSIONS: Our data provide clinical evidence that stroke patients with dorsal medulla involvement might present with bronchorrhea which seemed to be mediated via a parasympathetic mechanism. This is a treatable disease, and early diagnosis and treatment may greatly reduce patients’ suffering, avoid antibiotics abuse, reduce the incidence of aspiration pneumonia, and shorten the length of hospitalization.
Patel U, Agrawal M, Krishnan P, et al. Neuroleptic malignant syndrome presenting as pulmonary edema and severe bronchorrhea. J Natl Med Assoc 2002;94:279-282.
Neuroleptic malignant syndrome is a rare (incidence, 0.02%-3.2%) but dangerous complication following the use of neuroleptic drugs. When not promptly recognized, this disease carries a high mortality (10%-20%) and morbidity rate. We report an unusual case of neuroleptic malignant syndrome that presented predominantly with autonomic instability in the form of recurrent episodes of respiratory distress. The respiratory distress was initially caused by pulmonary edema and later was caused by severe bronchorrhea. We propose that aspiration pneumonia resulting in respiratory failure, the leading cause of death in neuroleptic malignant syndrome, may be a result of a combination of altered mental status and bronchorrhea. This has therapeutic implications because early institution of bromocriptine/dantrolene can prevent aspiration pneumonia and, hence, mortality from respiratory failure.
Remi C, Remi J, Bausewein C. Pharmacological Management of Bronchorrhea in Malignant Disease: A Systematic Literature Review. J Pain Symptom Manage 2016;51:916-925.
CONTEXT: Malignant respiratory tract tumors can lead to massive fluid production, known as bronchorrhea. This symptom can be very distressing itself, and it can lead to or aggravate other symptoms such as dyspnea and cough. Pharmacological treatment options have been reported in the literature. However, no systematic evaluation of their effectiveness has been conducted so far. OBJECTIVES: To systematically identify, appraise, and evaluate the effectiveness of symptomatic pharmacological treatment of bronchorrhea in malignant disease in palliative care. METHODS: A systematic literature review in Medline, Embase, and the Cochrane Database, as well as citation tracking, hand searches of selected journals, and reference lists of retrieved articles, was performed. For the purpose of this review, only symptomatic treatments were considered. RESULTS: No controlled clinical studies could be identified. Twenty of 48 retrieved references were analyzed in detail. These 20 case reports and case series dealt with the symptomatic pharmacological management of bronchorrhea in malignant disease; the other 28 had to be excluded for various reasons. The majority of patients suffered from bronchioloalveolar carcinoma. Reported treatments comprise corticosteroids, macrolide antibiotics, inhaled indomethacin, octreotide, and tyrosine-kinase inhibitors. For some drugs, significant clinical impact on distressing symptoms associated with bronchorrhea was reported. CONCLUSION: There are only very limited data on the pharmacological management of bronchorrhea in malignant disease. Because of the distressing nature of the symptom, a pragmatic management strategy is essential. This can include promising treatment options reported in the literature but should also take into account availability, individual tolerability, and costs. Further research is needed.
コメント：気管支漏の症例のほとんどがBACと診断されている。またBACに対する治療としてチロシンキ ナーゼ阻害薬の投薬は症状の緩和が見込める可能性が高い。気管支漏の第一選択の治療薬はコル チコステロイドとマクロライド系抗生物質であるが、BACと診断されたのであれば分子標的薬の 使用が好ましい。(兵庫ペット医療センター東灘病院 谷口哲也-2019.5.25 )
Abelleira R. Reversible diffuse lung disease after mycophenolate mofetil withdrawal. Pulmonology 2018;24:361-362. doi: 10.1016/j.pulmoe.2018.10.003
Mycophenolate mofetil(MMF) is a cell cycleinhibitor widely used in patients with solid organ transplants, in the treatment of many autoimmune diseases2,3and, even, in hypersensitivitypneumonitis. Its most frequent side effects are myelosuppression, gastrointestinal disordersand an increased susceptibility to infections, including pneumonia. The development of interstitial lung diseaseafter taking this drug is a rare adverse effect of which only isolated cases have been published. We present a patient with pulmonary toxicitydue to MMF.
Gemma A, Kusumoto M, Kurihara Y, et al. Interstitial Lung Disease Onset and Its Risk Factors in Japanese Patients with ALK-positive NSCLC Following Treatment with Crizotinib. J Thorac Oncol 2018.
INTRODUCTION: The study objective was to determine the incidence and characteristics of drug-induced interstitial lung disease (ILD) associated with an orally available small-molecule tyrosine kinase inhibitor, crizotinib in the real-world clinical setting. METHODS: Post-marketing surveillance was performed in Japan to obtain information on the safety and efficacy of crizotinib. Target patients included all patients with anaplastic lymphoma kinase-positive non-small cell lung cancer (NSCLC) who received crizotinib, during the enrollment period between May 2012 and December 2014. The observation period was 52 weeks. Expert analysis of the ILD incidence was performed by an ILD independent review committee composed of 5 medical specialists. RESULTS: The safety analysis set included 2,028 patients, and more than half of the patients (56.4%) were nonsmokers. The incidence of ILD associated with crizotinib therapy was 5.77%; and 3.45% patients showed grade >/=3. Pulmonary oedema-like shadows with or without diffuse alveolar damage pattern were observed in the crizotinib associated ILD (incidence: 0.39%), but a causal relationship with the prognosis could not be identified. The ILD developed within 4 weeks from initiation of crizotinib administration in 41.9% and within 8 weeks in 69.2% of the patients. Age >/=55 years, ECOG PS 2-4, smoking history, previous or concomitant ILD and comorbid pleural effusion were statistically determined as significant risk factors for crizotinib-induced ILD. CONCLUSIONS: Crizotinib therapy should be applied to the NSCLC patients with any of above risk factors under a cautious monitoring for ILD occurrence, and clinicians should pay attention to the risks of severe ILD.
齋藤 弘, 足立 雄, 山下 高, et al. 遷延する経過をたどった競技用白線石灰(炭酸カルシウム)吸入による慢性肺障害の1例. 日本呼吸器学会誌 2014;3:265-269. （PDFあり）
A 45-year-old man presented with chronic cough and dyspnea in August 200X－2 after putting white linepaint materials, mainly consisting of calcium carbonate, into a drawing assisting unit many times, without use of a face mask. He then used this unit to draw lines on the ground for setting up a car park. He had been followed up in another hospital, but when his dyspnea worsened in January 200X, he was referred to our hospital. A chest computed tomography revealed peripherally dominant ground-glass density in both upper lungs. We performed thoracoscopic lung biopsy of the left lung, and the biopsy specimens showed diffuse calcium deposits and many foreign giant cells in the alveoli. Inductively coupled plasma emission spectroscopy（ ICPS-8100, SHIMADZU） analyzed chemical elements of white line materials and specimens of his lung, which had almost the same elements. We diagnosed his lung injury as being caused by inhalation of the white line powder.
Jakubczyc A, Neurohr C. [Diagnosis and Treatment of Interstitial Lung Diseases]. Dtsch Med Wochenschr 2018;143:1774-1777.
Interstitial lung diseases compromise a group of diffuse predominantly chronic inflammatory and fibrosing disorders of the lung parenchyma. This article reviews practice-relevant publications on the diagnosis and treatment of idiopathic pulmonary fibrosis – the most common form of idiopathic interstitial lung diseases. The new patient questionnaire of the German Society of Pneumology facilitates collection of a complex case history of diverse interstitial lung diseases in individual patients. The Fleischner Society White Paper emphasize the importance of high-resolution computer tomography in the diagnosis of IPF. Histological diagnosis of the fibrotic changes is necessary in two situations: in case of CT findings indeterminate or suggestive for a diagnosis other than IPF and in case of inconsistence of medical history, laboratory findings and diagnostic imaging. The new international guidelines emphasize the importance of the interdisciplinary discussion prior to invasive diagnostic procedures, especially in the case of nonspecific interstitial lung changes. Bronchoscopy with lung cryobiopsy has gained importance in recent years. The recommendation to standardize this diagnostic method is speicified in a recently published expert opinion. The German Guideline for Idiopathic Pulmonary Fibrosis, published in 2017 suggests current therapeutic standards in this disease. The treatment with one of two registered antifibrotic drugs (pirfenidone, nintedanib) is to be started as soon as possible after the diagnosis and should be a long-term therapy. In case of intolerance or a significant progress of the disease despite the treatment, the therapy switching to an alternative drug may be considered. The combination of both therapies is not recommended. In current studies, new drugs are being tested (e. g. the serum protein pentraxin 2, antibodies against the growth factor CTGF). On the other hand, the efficacy of the registered antifibrotic medicaments, nintedanib and pirfenidone, in interstitial lung diseases other than idiopathic pulmonary fibrosis is being evaluated.
Jeny F, Brillet PY, Kim YW, et al. The place of high-resolution computed tomography imaging in the investigation of interstitial lung disease. Expert Rev Respir Med 2019;13:79-94. doi: 10.1080/17476348.2019.1556639
INTRODUCTION: High-resolution computed tomography (HRCT) has revolutionized the diagnosis, prognosis and in some cases the prediction of therapeutic response in interstitial lung disease (ILD). HRCT represents an essential second step to a patient’s clinical history, before considering any other investigation, including lung biopsy. Areas covered: This review describes the current place of HRCT in the diagnosis, prognosis and monitoring of ILD. It also lists some perspectives for the near future. Expert commentary: Since the 1980s, HRCT and its interpretation have improved, the diagnosis value of patterns, and the integration of bio-clinical elements to HRCT have been better standardized. The interobserver agreement has been investigated, allowing a better use of some limits in the interpretation of various signs. It not only takes into account one particular predominant sign, but the combination of patterns and the distribution of findings. Thanks to HRCT, the range of diagnoses and their probability are more accurately identified. The contribution of HRCT has been optimized during the multidisciplinary discussion that a difficult diagnosis calls for. HRCT quantification of the extent of diffuse lung disease becomes possible and is linked to prognosis. In the future, artificial intelligence may significantly modify the practice of radiology.
van Manen MJ, Birring SS, Vancheri C, et al. Cough in idiopathic pulmonary fibrosis. Eur Respir Rev 2016;25:278-286. doi: 10.1183/16000617.0090-2015.
Many patients with idiopathic pulmonary fibrosis (IPF) complain of chronic refractory cough. Chronic cough is a distressing and disabling symptom with a major impact on quality of life. During recent years, progress has been made in gaining insight into the pathogenesis of cough in IPF, which is most probably “multifactorial” and influenced by mechanical, biochemical and neurosensory changes, with an important role for comorbidities as well. Clinical trials of cough treatment in IPF are emerging, and cough is increasingly included as a secondary end-point in trials assessing new compounds for IPF. It is important that such studies include adequate end-points to assess cough both objectively and subjectively. This article summarises the latest insights into chronic cough in IPF. It describes the different theories regarding the pathophysiology of cough, reviews the different methods to assess cough and deals with recent and future developments in the treatment of cough in IPF.
コメント: IPFにおける咳の発症は「多因子性」である可能性が最も高く、物理的、生化学的および神経感覚的な変化による影響を受けている。物理的な変化としては、線維症によって引き起こされる肺の力学的変形がRARやSARといった物理刺激に敏感な神経線維に直接影響を与えうる。生化学および神経感覚的変化として、IPF患者の痰により多く含まれる神経栄養因子の関与が考えられる。神経栄養因子は、特発性間質性肺炎の患者の肺で発現が増加していて、これによる咳反射の神経への影響が示唆される。併発疾患、特に胃食道逆流症も重要な役割を果たしていると考えられ、咳受容体は、喉頭および上気道における胃分泌物の吸引によって直接刺激される可能性がある（動物病院川越 中野秀哉-2018.12.29)。
Vigeland CL, Hughes AH, Horton MR. Etiology and treatment of cough in idiopathic pulmonary fibrosis. Respir Med 2017;123:98-104. doi: 10.1016/j.rmed.2016.12.016. Epub 2016 Dec 24.
Idiopathic pulmonary fibrosis (IPF) is a progressive disease of dysregulated wound healing leading to unremitting scarring and loss of lung function. The predominant symptoms are dyspnea on exertion and a persistent dry cough. For patients with IPF, cough is more than just bothersome; it has a significant negative impact on quality of life and is a marker of disease severity and progression. The etiology of cough in IPF is unclear but may be due to architectural distortion of the lungs, increased sensitivity of the cough reflex, airway inflammation, or changes in mucus production and clearance. There also may be an overlap between IPF cough and cough due to other common etiologies such as asthma, gastroesophageal reflux disease, upper airway cough syndrome, and medications. There are no approved therapies to specifically treat IPF cough, and recently approved medications for IPF have not been evaluated in cough. Few clinical trials have focused on treatments for IPF cough. To date, there is only one randomized, placebo control therapeutic study for IPF cough with thalidomide, which significantly reduced IPF cough and improved quality of life. Two additional cohort studies report that interferon-α and prednisolone also decrease IPF cough. However, no medication is approved to treat IPF cough. Currently, the mainstay of therapy for IPF cough is standard cough suppressants, which have limited efficacy and often intolerable side effects. Future studies are needed to determine an effective therapy to alleviate this particularly debilitating symptom and improve overall quality of life for patients suffering with IPF.
コメント: IPF患者における咳の原因は不明である。可能性としては肺の構造的な変化、咳反射の感受性増加、気道の炎症、粘液産生とクリアランスの変化が挙げられる。IPF患者の咳はIPFだけが原因でなく、喘息、胃食道逆流、後鼻漏などの併発疾患や薬剤による咳との重複もありうる（動物病院川越 中野秀哉-2018.12.29)。
Bargagli E, Di Masi M, Perruzza M, et al. The pathogenetic mechanisms of cough in idiopathic pulmonary fibrosis. Intern Emerg Med 2018. 2018 Sep 29. doi: 10.1007/s11739-018-1960-5.
Idiopathic pulmonary fibrosis is a peripheral subpleural interstitial lung disorder limited to the lung not involving the airways. It has a poor prognosis (survival less than 5 years) and commonly an interstitial pneumonia radiological pattern. Patients complain of a chronic dry cough in 80% of cases. A cough is often the first symptom of this rare disease, preceding dyspnea by years, and is associated with a poor prognosis, high dyspnea scores and low FVC percentages. The pathogenetic mechanisms leading to coughing in IPF are unclear. This review focuses on recent evidence of cough pathophysiology in this disease. Gastroesophageal reflux may promote coughing in IPF patients; bile salts and pepsin may be abundant in BAL of these patients, inducing overproduction of TGF-β by airway epithelial cells and mesenchymal transition with fibroblast recruitment/activation and extracellular matrix deposition. Patients have an enhanced cough reflex to capsaicin and substance P with respect to control subjects. Moreover, patients with the MUC5B polymorphism show more severe coughing as MUC5B encodes for the dominant mucin in the honeycomb cysts of IPF patients. Comorbidities, including asthma, gastroesophageal reflux, hypersensitivity pneumonitis, bronchiectasis, chronic obstructive pulmonary disease and emphysema, can induce coughing in IPF patients. There is no clear explanation of the causes of coughing in IPF. Further research into the pathophysiology of IPF and the pathogenetic mechanisms of coughing is necessary to improve survival and quality of life.
コメント: IPF患者のBALでは胆汁塩やペプシンが豊富に認められうるが、胆汁塩やペプシンは、気道上皮でのTGF-βの過剰産生と間葉転換を誘導することが知られている。このことから、胃食道逆流がIPF患者の咳を助長する可能性がある（動物病院川越 中野秀哉-2018.12.29)。
Andoh Y, Aikawa T, Shimura S, et al. Morphometric analysis of airways in idiopathic pulmonary fibrosis patients with mucous hypersecretion. Am Rev Respir Dis 1992;145:175-179. （PDFあり）
Five idiopathic pulmonary fibrosis (IPF) patients with sputum since the initial period of the disease (IPF SP+, more than 15 ml/day) were compared with five IPF patients without sputum throughout the course of the disease (IPF SP-) and four control subjects without pulmonary disease matched for age and sex. No significant differences in the duration of symptoms, pulmonary functions, or glucocorticoid therapy were observed between the two IPF groups. Autopsied lungs fixed by immersion into formaldehyde were used for morphometry by digitizing computer. The volume proportion of glands to bronchial wall thickness (gland%), volume proportion of goblet cells to total epithelial layer (goblet%), and luminal mucous volume were measured in central and peripheral airways. The gland percentage in the central airways of the IPF SP+ group was 18 +/- 1% (mean +/- SE), which was significantly greater than 7 +/- 0.6% of the IPF SP- group (p less than 0.001), similar to the 6 +/- 1% of control subjects. Luminal mucous volume in the peripheral airways of the IPF SP+ group was 11 +/- 2%, which was significantly greater than 3 +/- 1% of the IPF SP- group (p less than 0.05) or 0.6 +/- 0.3% of the control subjects (p less than 0.01). Furthermore, luminal mucous volume in both the central and peripheral airways significantly correlated with gland% (p less than 0.01, each). No significant difference in other parameters such as goblet% and cell infiltration between the IPF SP+ group and IPF SP- group was observed. These findings suggest that IPF with hypersecretion is associated with mucous glandular hypertrophy and the accumulation of mucus in the airways.
コメント：ヒトIPF患者では喀痰の増量のため湿性咳が認められる場合がある。IPFでは肺実質病変に関心が向きがちだが、この研究では気道の形態変化について調べてみた。性別と年齢をマッチングさせ、5例の湿性咳を示すIPF患者、5例の乾性咳を示すIPF患者、および肺疾患のないコントロール群４例の剖検肺標本より気道の病理組織所見を比較した。有症期間、肺機能、ステロイド投与量に両IPF患者群に有意差はなかった。気道表面全体に占める杯細胞の比率（goblet%）と粘液中細胞数に両IPF患者群間に有意差はなかったが、中枢気道のおける気道壁厚に対する気管支腺の占有率（気管支腺比率）が、湿性咳IPF群で他2群に比べ有意に高く（18±1％、vs 乾性咳IPF群：7±0.6％、コントロール群：6±1％、ともにP＜0.001）、末梢気道内の粘液量は湿性咳IPF群で他2群に比べ有意に高く（11±2％、vs 乾性咳IPF群：3±1％、コントロール群：0.6±0.3％、ともにP＜0.01）、この粘液量の増加は中枢気道でも末梢気道でも気管腺比率と高い相関を示した（ともにp＜0.01）。これらの結果から、気道分泌過剰を示す IPFは、気道内における気管支腺増生と粘液量の増加と関連があると考えられた（犬・猫の呼吸器科 城下-2019.1.1）。
平島 智, 大畑 一, 玉野井 優. 粘液貯留に起因する多発性の気管支結石の1例. 日本胸部疾患学会雑誌 1993;31:79-83. （PDFあり）
The patient was a 57-year-old male with long-standing bronchiectasis who developed severe respiratory failure and died in 1991. Autopsy revealed multiple broncholithiasis in both lungs, but no calcified lymph nodes in the hilar region. Since histological examination of the broncholiths showed only stratified structures but no tissue structure, most likely cause was casidered to be calcification of mucus in the bronchi. Analysisof the stone components revealed 78% calcium and 22% protein. This patient represents a case of multiple broncholithiasis caused by mucus retention, which is thought to be very rare.
気管支結石症は本邦において森,篠井らの報告以来140例報告されている.今回我々は気管支拡張症に慢性呼吸不全を合併し急性増悪の為死亡,その後剖検となった57歳男性の症例を経験した. 剖検の結果, 両側肺の下葉を中心に多発する気管支結石を認めた. 肺内肺門縦隔リンパ節,他臓器の石灰化を認めなかった.本例の気管支結石は層状構造を示し, 弾力線維染色および銀線維染色でリンパ節や肺組織をうかがわせる所見を認めず, 拡張した気管支に一致して形成されていた. 以上の所見から本例は気管支拡張症の粘液貯留に起因する多発性気管支結石と考えられた. 同様の症例は検索した範囲では認めず, 極めて稀な症例と思われた. また結石の成分は炭酸カルシウム78%,蛋白質22%であった. 分泌物貯留に起因する気管支結石では, 炭酸カルシウムを主成分にすることが多いという報告に一致した.
朝川 勝, 島田 昌, 蛇澤 晶, et al. 【非腫瘍性気道病変のすべて】 閉塞性細気管支炎ならびに全身性疾患に伴う気道病変、その他 その他 気管支結石症. 日本胸部臨床 2012;71:S291-S295. （PDFあり）
Talavera J, del Palacio MJ, Bayon A, et al. Broncholithiasis in a cat: clinical findings, long-term evolution and histopathological features. J Feline Med Surg 2008;10:95-101 doi: 10.1016/j.jfms.2007.06.012
A 14-year-old neutered male Persian cat was evaluated because of an acute exacerbation of a chronic cough of 2-3 years of duration. Physical examination was normal except for the auscultation of accentuated breath sounds and wheezes cranially on both sides of the chest. Complete blood count, biochemical parameters and urinalysis were normal. Thoracic radiographs showed a generalised nodular pattern with multiple mineral opacities. Oral prednisone and doxycycline were prescribed. Two weeks later, the frequency of the cough was significantly reduced. Terbutaline was recommended for relief of acute exacerbations. Three years later the cat was evaluated again due to a non-related disease that led to the euthanasia of the cat. Concerning its respiratory disease, the cat had experienced nearly asymptomatic periods of 3-6 weeks of duration punctuated by acute exacerbation periods of 7-10 days, during which terbutaline was useful to relieve the cough. Thoracic radiographs showed a mild increase in the size and extent of the pulmonary mineralisation. Histopathologically, mild bronchitis and bronchiectasis were evident, accompanied by calcified bronchial plugs and marked hyperplasia and hypertrophy of the seromucinous glands. Based on clinical and pathoanatomical findings, a final diagnosis of miliary broncholithiasis and bronchiectasis was made. Broncholithiasis should be considered in differential diagnosis of pulmonary mineralisation in cats. When no concomitant diseases are present, this rare disease appears to have a slowly progressive evolution that does not appear to carry a bad prognosis and may be satisfactorily managed with combinations of bronchodilators and corticosteroids.