犬・猫の呼吸器臨床研究会

猫のびまん性肺疾患(FDLD)研究班の報告(2019.3.22更新 計32)

猫の消えない肺浸潤影の病態や自然経過/診療手順/治療法と成績、気道分泌物過剰と肺病理との関連の文献レビュー

テーマは、「猫のブロンコレア23例」

猫のIPF様疾患関連文献


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.

猫の特発性肺線維症様疾患の同定と特徴

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.

コメント1:UIPの組織学的基準を示す23匹の剖検の後ろ向き研究において6頭が肺腫瘍(4頭が気管支肺胞腺癌、1頭が多病巣性腺腫のある限局性癌腫、残り一頭は組織球性肉腫)と診断された。しかし、そのうちの4頭がはじめの組織学的診断として腫瘍と診断されたものが、剖検の結果、最終的には腫瘍ではなくUIPに関連する過形成と異形成の変化と考えられた。線維性間質性肺炎と肺腫瘍が同時に存在する理由の仮説としては,上皮過形成の腫瘍への進行、線維性変化および腫瘍性形質転換の共有病因危険因子、ならびにびまん性炎症による発癌の誘導が含まれる。重度の肺線維症の変化と腫瘍の変化との区別は困難であることを示唆している(代官山動物病院 明石依里子-2018.12.1)。

コメント2:猫においても人のIPFのような肺の線維性障害が認められている。猫の他の多くの気管支疾患と異なり、主に吸気性または両相性の呼吸困難を呈する。一般検査での診断は困難であり、除外診断と最終的には肺生検が必要である。抗炎症・免疫調整などの治療が試みられるが、人同様治療成績は悪い(ダクタリ動物病院東京医療センター 山下弘太-2019.1.12)。


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.

猫の自然発症性特発性肺線維症-Ⅱ型肺胞上皮細胞の形態と微細構造の異常

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.

コメント:人での間質性肺炎パターンと同じように、Ⅱ型肺胞上皮細胞と筋線維芽細胞は猫の特発性肺線維症の細胞構成に重要な存在である。Ⅱ型細胞の超微細構造は猫のIPFがⅡ型肺胞上皮細胞の異常に関連していることを示唆している(代官山動物病院 明石依里子-2018.12.1)。


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.

猫の非定型びまん性線維化肺疾患の1例

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.

コメント1:全体的な牽引性気管支拡張やキメの荒い網状陰影があり、人では重度な線維化をおこしていると認識されるものにもかかわらず、この猫はCT検査から5ヶ月生きた。これは前に報告されたIPFの猫の生存期間5.5ヶ月と一致した。人ではステロイド、コルヒチン、血栓薬、シクロスポリン、ボセンタン(エンドセリン受容体拮抗剤)、エネルセプト、ピルフェリドンでの治療は推奨されていない。アセチルシステインや高濃度酸素、肺移植で効果があったとの報告が人ではある。大抵猫は侵襲性のある呼吸器診断のための処置や検査で悪化しているので鎮静や覚醒下CTが麻酔下よりも推奨される(代官山動物病院 明石依里子-2018.12.1)。

コメント2:猫の特発性肺線維症と考えられる症例があったが、従来考えられていた組織学的な特徴、分布とは異なっていた。猫においてはより良い分類が必要かもしれない(ダクタリ動物病院東京医療センター 山下弘太-2019.1.12)。


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.

米胸部学会(ATS)ワークショップレポート:人と家畜での線維化性肺疾患の比較病理

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.

コメント:ヒトと家畜の線維化肺障害を比較することで、種間の類似性や相違点をよりよく理解でき、自然発生する線維性肺疾患の根本的なメカニズムを考察することができうるであろう(代官山動物病院 明石依里子-2018.12.1)。


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)


 

猫の肺の画像所見と病理との連関に関する文献


Henninger W. Use of computed tomography in the diseased feline thorax. J Small Anim Pract 2003;44:56-64.   (PDFあり)

猫の胸部疾患におけるCTの使用について

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.

犬と猫の非心臓性の胸腔内疾患に対するCT検査の使用について

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.

コメント:胸部CT検査がX線検査による鑑別に影響を与えるかを病理組織検査をもとに検討した。CT検査によって13/28の犬と3/5の猫でX線画像診断より追加の情報が得られた。特に縦隔内腫瘍についてはX線検査で肺病変と診断されていたが、CT検査で縦隔内腫瘤であることが明らかになった症例が多かった。また胸腔内リンパ節腫大が腫瘍を示唆する所見であるが、気管気管支リンパ節がCT検査で異常がなかった症例でも病理組織検査で浸潤を認めたこともあった(兵庫ペット医療センター東灘病院 谷口哲也-2019.3.22)。


Secrest SA, Bailey MQ, Williams KJ, et al. Imaging diagnosis–Feline idiopathic pulmonary fibrosis. Vet Radiol Ultrasound 2008;49:47-50. (PDF)

画像診断-猫の特発性肺線維症

No abstract(本文より抜粋)

“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.”

コメント:線維芽細胞や筋繊維芽細胞を主体とした間質の多巣性に分布する線維化、肺胞上皮細胞の過形成、間質の平滑筋の異形成や過形成、炎症反応の欠如が認められ、UIPに言及されるものと一致した。そして人の間質性肺炎のよくみられる変化としての2型肺胞細胞の超微細構造も猫の肺線維症のものと近似していた。これは遺伝的な2型上皮細胞の異常とこの病気が関連している可能性を示唆する(代官山動物病院 明石依里子-2018.12.1)。


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.

猫肺線維症9例のX線および病理組織学所見

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.

コメント:9頭中、すべての症例で肺線維化、2型肺胞上皮細胞の過形成、平滑筋の肥厚が認められた、上皮細胞の異形成は一頭でのみ認められた(代官山動物病院 明石依里子-2018.12.1)。


 


猫の肺疾患に関する文献(原因が確定した猫の間質性肺疾患)


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.

高蓄積量のニトロウレア化学療法後に生じた猫の肺線維症

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.

コメント:ニトロウレア化学療法によって肺線維症を発症する可能性がある(ダクタリ動物病院東京医療センター 山下弘太-2019.1.12)。


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.

H1N1インフルエンザウイルス暴露後に急性気管支間質性肺炎を発症した室内飼育ネコの2

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.

コメント:インフルエンザAH1N1はヒトから猫に伝播する可能性があり、症状は重篤になり得る(ダクタリ動物病院東京医療センター 山下弘太-2019.1.12)。


Drolet R. Disseminated tuberculosis caused by Mycobacterium avium in a cat. J Am Vet Med Assoc 1986;189:1336-1337.

猫の全身播種型抗酸菌症の一例

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)


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.

2ヶ月齢猫に生じた致死的な肺炎連鎖球菌関連蜂窩織炎

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.

コメント:剖検例。PCRにて診断(ペット家族動物病院西五反田店 近藤絵里子-2019.2.7)


Bennett AD, Lalor S, Schwarz T, et al. Radiographic findings in cats with mycobacterial infections. J Feline Med Surg 2011;13:718-724.

猫の抗酸菌感染症33例の胸部X線検査所見

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.

コメント:胸部X線検査による評価。培養またはインターフィロン-γ遊離試験によって診断(ペット家族動物病院西五反田店 近藤絵里子-2019.2.7)


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.

腸管外性病原性大腸菌感染による劇症肺炎に罹患した若齢猫の一例

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。転機:死亡( ペット家族動物病院西五反田店 近藤絵里子-2019.2.7)


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)

シクロスポリン投与歴のある猫におけるサルモネラ属菌感染による肺炎の1例

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。転機: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 )


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)

抗酸菌感染症の猫20例のCT所見

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 )


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)

イタリアにおけるアビシニアン集合飼育所におけるMycobacterium bovisによる結核症の集団発生

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 )


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.

Mycobacterium bovis感染による猫の全身性結核症の一例

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)


猫の間質性肺疾患(総論、レビュー)

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)。


 

猫のブロンコレア


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.

5年間で、ゼロ音、慢性咳、慢性努力呼吸、消失しない肺浸潤影、気管支鏡検査にて気道分泌物過剰を示す猫18例を経験した。ロシアンブルーで多く、散発的湿咳、低酸素血症、気道感染なく、肺野CT検査で腫瘤状/多発囊胞性陰影、肺病理検査で気管支腺増生、間質性肺炎、細気管支肺胞上皮癌、腺癌、気管支結石を認めた。60日生存率は72.2%、中央生存期間は361日間、無処置2例は9日間であった。肺葉切除術とステロイド投与が有効であった。初診時年齢10歳未満とCT検査で胸部リンパ節腫大なしは予後良好、CT検査で胸部リンパ節腫大ありと無処置は予後不良と考えられた。人の気管支ろうに相当するが猫特有の肺疾患かもしれない。

コメント:猫で気道分泌物過剰を特徴とする疾患ですが、間質性肺炎との関連が示唆されます。しかし、細気管支肺胞上皮癌(BAC)や腺癌とも関連があり、気管支結石形成が高率に認められます。予後はかならずしもよくなく、病態解明とともに治療法の確立が急がれると思われます(犬・猫の呼吸器科 城下−2018.11.28)


 

ヒトのブロンコレア


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.

コメント:エリスロマイシンはin vitroでヒトの気道の粘液分泌を抑制することが知られている。高用量のグルココルチコイドならびにテオフィリンの内服、β作動薬の吸入を行なっても気道分泌物過剰をコントロールできなかった65歳白人男性にエリスロマイシンの内服を追加したところ著しい改善が認められた。12時間の粘液分泌量は200ml以上から50ml以下に減少し、マクロファージ由来分泌促進物質、気道上皮由来の粘液糖蛋白の減少も認められた。メサコリン吸入試験(気道の過敏性を定量的に評価するための試験)は陰性となった。

本研究では血管作動性腸管ペプチドに対する自己抗体の有意な減少を報告している。血管作動性腸管ペプチドは上皮細胞に対する強力な分泌抑制効果を持つため、筆者らはこのペプチドが気道過分泌のメカニズムにな重要な役割を果たしているのではないかと考えている。

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 )


 

猫のゴロゴロ音の鑑別疾患


掲載準備中


 

人のびまん性肺疾患の鑑別疾患


総論

 


各論

Abelleira R. Reversible diffuse lung disease after mycophenolate mofetil withdrawal. Pulmonology 2018;24:361-362. doi: 10.1016/j.pulmoe.2018.10.003

ミコフェノール酸モフェチル投与中止にて改善したびまん性肺疾患

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.

コメント:ヒトにおいてミコフェノール酸モフェチルの投与は間質性肺疾患を引き起こす可能性がある。過去の報告では投与開始後18か月以内に発症していたが、数年以上経過してから発生する例が認められた。本症例では休薬によって改善が得られた(ダクタリ動物病院東京医療センター 山下弘太-2019.1.12)。


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.

クリゾチニブ治療後のALK陽性NSCLCの日本人患者における間質性肺疾患発症とその危険因子

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.

コメント:チロシンキナーゼ阻害剤であるクリゾチニブは薬物誘発性間質性肺炎を引き起こす可能性がある。発症する場合は約70%は投与開始後8週間以内に発症が見られ、有意な危険因子は年齢55歳以上、ECOGパフォーマンスステータス2-4、喫煙、ILD罹患歴、胸水であった(ダクタリ動物病院東京医療センター 山下弘太-2019.1.12)。


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.

症例は45歳、男性。x-2年8月に駐車場に白線を引くため、狭い倉庫内でマスクをせずに競技用白線石灰(炭酸カルシウム)を容器に移し替える作業をした。当日夜より咳嗽が出現し、他院で経過をみられていたが呼吸困難を認めるようになり、x年1月に精査目的で総合病院土浦協同病院呼吸器内科に紹介入院した。胸部ctでびまん性に末梢側優位のすりガラス陰影を認め、胸腔鏡下肺生検組織で肺胞内にカルシウム沈着と異物巨細胞の集簇を多数認めた。白線用の石灰と生検検体の元素分析結果が一致し、石灰吸入による慢性肺障害と診断した。貴重な症例と考え報告する。(著者抄録)

コメント:粘液由来気管支結石の成分に炭酸カルシウムが多いのですが、外因性要因もあるかもしれません。炭酸カルシウム自体に間質性肺炎を生じる慢性肺毒性があるかもしれません。猫砂に炭酸カルシウムを含むものがあり、砂の煙の慢性吸入と肺障害との関連の可能性があります(犬・猫の呼吸器科 城下−2019.1.16)


人の特発性間質性肺炎(IIPs


Jakubczyc A, Neurohr C. [Diagnosis and Treatment of Interstitial Lung Diseases]. Dtsch Med Wochenschr 2018;143:1774-1777.

間質性肺疾患の診断と治療

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.

コメント:特発性肺線維症(IPF)の診断と治療に関するレビュー。診断においては高解像度CTが有用である。CTで確定できないまたはIPF以外の疾患が示唆される場合、または病歴やその他の検査所見がCT所見と一致しない場合に組織学的診断が必要であると勧告されている。気管支鏡検査による肺凍結生検は重要性を増し、標準化されつつある。抗線維化薬(ピルフェニドンまたはニンテダニブ)は診断後できるだけ早くかつ長期的に使用されるべきである。効果が認められなければ薬剤変更を行うべきである(ダクタリ動物病院東京医療センター 山下弘太-2019.1.12)。


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

間質性肺疾患検査における高分解能コンピュータ断層撮影の位置づけ

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.

コメント:ILDの診断と予後の判断に高解像度(HR)CTが有用である(ダクタリ動物病院東京医療センター 山下弘太-2019.1.12)。


 

人の間質性肺炎/特発性肺線維症(IPF)での乾咳の理由


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.

特発性肺線維症における咳

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.

特発性肺線維症における咳の病因と治療

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.

特発性肺線維症における咳の病態メカニズム

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)。


 

人のBACが肺炎様所見を示す理由


掲載準備中


 

気道分泌物過剰と間質性肺疾患/特発性肺線維症(IPF)との関連


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)

粘液分泌過剰を示すヒトの特発性肺線維症患者肺の剖検標本による気道の形態異常の解析

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)。


 

気管支結石と気道分泌物過剰


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.

コメント:気道内粘液貯留と炭酸カルシウムを主成分とする気管支結石との関連を示唆する論文(犬・猫の呼吸器科 城下-2019.1.16)


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)

気管支結石症はまれな疾患であり、古くから散発的に症例の報告がなされてきたが、結石の由来を石灰化リンパ節としているものが多い。しかし、われわれの症例では粘液由来結石が半数を占め、リンパ節由来は少数であった。本症の病態解明には結石の由来を明らかにすることが不可欠であり、結石の病理学的検索がこれに役立つものと考える。(著者抄録)

コメント:人の気管支結石は粘液由来結石が半数を占め、それはHE染色で層状構造を示し、EVG染色および鍍銀染色で肺組織やリンパ節を思わせる構造を認めない。これまでの粘液由来結石の報告では、析出物質の過飽和・鬱滞・炎症の3条件が結石の発生に必要とされるとか、分泌物の鬱滞および粘膜の慢性炎症を伴う気管支拡張や、分泌物の流出が不十分な空洞において結石ができやすいことなどが、指摘されている。病理組織学的には、結石内部に層状構造を認める(犬・猫の呼吸器科 城下−2019.1.16)。


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

猫の気管支結石症:臨床所見、長期的進展、病理組織学的特徴

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.

コメント:緩徐に進行する猫の気管支結石症の1例。慢性咳あり。剖検にて、気管結石周囲の気管支壁内には気管支腺の著しい過形成と増生を認めた。1例報告だが、猫の気管支結石と粘液過剰との関連を示唆している(犬・猫の呼吸器科 城下-2019.1.16)。