Propionibacterium acnes-associated sarcoidosis complicated by acute bird-related hypersensitivity pneumonitis.

BACKGROUND: The number of reports on sarcoidosis complicated by hypersensitivity pneumonitis (HP) is limited, and most describe cases complicated by chronic bird-related HP. Here, we present for the first time a case with Propionibacterium acnes-associated sarcoidosis complicated by acute bird-related HP. CASE PRESENTATION: A 62-year-old man with a past medical history of sarcoidosis was admitted to our department, and chest computed tomography showed diffuse ground-glass opacities, which appeared as he rapidly increased the number of pigeons he kept for a competition. Random transbronchial lung biopsy revealed well-formed non-caseating epithelioid granulomas, which contained positively stained substances on immunohistochemistry using the PAB antibody, a specific monoclonal antibody against P. acnes lipoteichoic acid. Poorly formed non-caseating granulomas without positively stained substances were also detected. CONCLUSION: We describe the successful identification of this exceptionally rare case of sarcoidosis complicated by acute bird-related HP in which two morphologically and immunohistologically different types of granulomas were present in the same lung.

Utility of budgerigar/pigeon/parrot-specific IgG antibody with ImmunoCAP® in bird-related hypersensitivity pneumonitis caused by other bird species and duvet.

BACKGROUND: Bird-related hypersensitivity pneumonitis (BRHP) is an extrinsic allergic alveolitis caused by inhalation of bird antigens. Although the measurement of serum-specific IgG antibodies against budgerigar, pigeon, and parrot with ImmunoCAP® is available in Japan, the utility of the test for patients with causes by bird breeding other than these three species, including contact with wild birds/poultry/bird manure, and use of a duvet is unknown. METHODS: Of the 75 BRHP patients who participated in our previous study, 30 were included. Six cases were caused by bird breeding of species other than pigeon, budgerigar, and parrot, seven were in contact with wild birds/poultry/bird manure, and 17 were using a duvet. Bird-specific IgG antibodies were compared among the patients, 64 controls, and 147 healthy participants. RESULTS: In patients with BRHP caused by bird breeding, budgerigar and parrot-specific IgG levels were significantly higher than in disease controls. Only parrot-specific IgG was significantly higher than in disease controls in patients caused by duvet use. However, among patients with acute episodes (acute and recurrent type of chronic BRHP), IgG antibodies against all three species were significantly higher than those of disease controls caused by bird breeding and the use of a duvet. CONCLUSIONS: Bird-specific IgG antibody with ImmunoCAP® was useful for screening and diagnosing BRHP caused by other bird species and duvets.

Pilot Study Using Recombinant Antigens r-PROE and r-IGLL1 for the Serodiagnosis of Feather Duvet Lung.

BACKGROUND: Feather duvet lung (FDL) is an underestimated form of acute and chronic hypersensitivity pneumonitis. Serological tests for FDL need to be validated. We investigated the ability of recombinant pigeon Proproteinase E (r-PROE) and Immunoglobulin-lambda-like-polypeptide-1 (r-IGLL1) proteins to support the serological diagnosis of FDL, and propose them as a serological tool for clinicians to differentiate cases from FDL and Bird fancier's lung (BFL). METHODS: Specific IgG antibodies against r-PROE and r-IGLL1, analyzed with ELISA, were measured in patients diagnosed with FDL (n=31), BFL (n=15) controls exposed (n=15) and unexposed to feathers (n=15). RESULTS: The sensitivity and specificity of the r-PROE ELISA for the serological diagnosis of FDL cases versus exposed and unexposed controls were 74.2% and 86.7% respectively, with an index threshold of 0.5 (AUC: 0.89). In addition, this serological test was effective to support the serological diagnosis of FDL and BFL cases with significantly different thresholds. The r-IGLL1 ELISA was only effective for the serological diagnosis of BFL. Also, these two serological tests were useful for the diagnosis of both chronic and acute forms. CONCLUSIONS: The new diagnostic test for FDL using r-PROE protein should help to detect overt and hidden cases of FDL. The combination of both test will help the clinician in distinguish between the etiology of birds or feathers duvet.

[A relapse of acute bird-related hypersensitivity pneumonitis due to the use of a feather duvet by a housemate].

In December 2007, a 78-year-old woman was admitted to our hospital complaining of cough and low-grade fever for 1 month. We performed various medical tests and diagnosed acute hypersensitivity pneumonitis. We suspected that the cause of illness was the prolonged use (10 years) of a feather duvet. She was treated with corticosteroids and was advised to avoid using feather duvets. This treatment improved her symptoms. However, she relapsed after 1 year. She had never used a feather duvet since the last admission, but her housemate used a feather duvet in the same room during winter. Bronchoalveolar lavage revealed lymphocytosis. Specific antibodies against pigeon and budgerigar-dropping extracts were present in her serum. On the basis of these findings, we diagnosed acute bird-related hypersensitivity pneumonitis. This condition is rarely caused by indirect exposure. Therefore, we reiterate the significance of obtaining of a detailed medical history to identify relevant antigens.

Feather duvet lung.

A 43-year-old non-smoker was referred with a 3-month history of malaise, fatigue and breathlessness. Blood avian precipitins were strongly positive. Lung function testing confirmed a restrictive pattern with impaired gas transfer. A 'ground glass' mosaic pattern was seen on CT imaging, suggestive of hypersensitivity pneumonitis. Although he had no pet birds, on closer questioning he had recently acquired a duvet and pillows containing feathers. His symptoms, chest radiograph and lung function tests improved after removal of all feather bedding, and he was also started on oral corticosteroid therapy. Our case reinforces the importance of taking a meticulous exposure history and asking about domestic bedding in patients with unexplained breathlessness. Prompt recognition and cessation of antigen exposure may prevent the development of irreversible lung fibrosis.

Pathogenesis of cBFL in common with IPF? Correlation of IP-10/TARC ratio with histological patterns.

BACKGROUND: A Th1 predominant immune response has been shown in acute hypersensitivity pneumonitis. Predominance of Th2 appears to favour the development of pulmonary fibrosis through the profibrotic process and has been described as crucial in the progression of idiopathic pulmonary fibrosis. Chronic bird fancier's lung (cBFL) can present with a histological pattern of usual interstitial pneumonia (UIP)-like lesions. Little is known about the Th1/Th2 balance in the pathogenesis of cBFL. METHODS: To evaluate the relevance of Th1-type chemokines (interferon-inducible protein, IP-10) and Th2-type chemokines (thymus- and activation-regulated chemokine, TARC) and their receptors (CXCR3 and CCR4) to the histological patterns of cBFL, 40 patients with cBFL who underwent surgical lung biopsies, 12 with acute BFL (aBFL) and 10 healthy volunteers were analysed. IP-10 and TARC levels in serum and bronchoalveolar lavage (BAL) fluid were measured by ELISA. Immunohistochemistry for CXCR3 and CCR4 was performed on surgical lung specimens. RESULTS: The ratio of TARC to IP-10 in the serum of patients with UIP-like lesions was significantly higher than in patients with cNSIP/OP-like lesions, aBFL and healthy volunteers. The ratio of CCR4 to CXCR3 in patients with UIP-like lesions was significantly higher than in those with cNSIP/OP-like lesions and fNSIP-like lesions. The ratio of CCR4-positive to CXCR3-positive cells correlated with the ratio of TARC to IP-10 in serum. CONCLUSIONS: A Th2 predominant immune response may play an important role in the development of UIP-like lesions, as already observed in idiopathic pulmonary fibrosis. A Th1 predominance may play a role in the development of cNSIP/OP-like lesions in cBFL.

Hypersensitivity pneumonitis secondary to lovebirds: a new cause of bird fancier's disease.

Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease due to the repetitive inhalation of antigens. Most new cases arise from residential exposures, notably to birds, and are thus more difficult to recognise. The present authors report a 59-yr-old male who complained of dyspnoea and cough while being treated with amiodarone. Pulmonary function tests revealed restriction and obstruction with low diffusing lung capacity for carbon monoxide and partial pressure of oxygen. A high-resolution computed tomography chest scan and bronchoalveolar lavage showed diffuse bilateral ground-glass attenuation and lymphocytic alveolitis, respectively. Initial diagnosis was amiodarone pulmonary toxicity, but because of a rapidly favourable evolution, this diagnosis was questioned. A careful environmental history revealed a close contact with lovebirds shortly before the onset of symptoms. Precipitins were strongly positive against lovebird droppings, but were negative against other avian antigens. The patient was diagnosed with hypersensitivity pneumonitis to lovebirds. Avoidance of lovebirds and steroid treatment led to rapid improvement. The present observation identifies a new causative agent for hypersensitivity pneumonitis and highlights the importance of a thorough environmental history and of searching for precipitins against antigens directly extracted from the patient's environment. These two procedures should allow a more precise classification of some cases of pneumonitis, and thus might avoid progression of active undiagnosed hypersensitivity pneumonitis to irreversible fibrosis or emphysema.

[Case of acute bird fancier's lung caused by a yellow-shouldered Amazon bird associated with lung cancer].

A 69-year-old man was admitted to our hospital complaining of generalized weakness and cough for one month. Chest computed tomography (CT) demonstrated bilateral ground-glass opacities and a nodule in right S6 about 11mm in diameter with multiple mediastinal lymph node swellings. After admission the patient's symptoms improved without therapy and examination of the bronchoalveolar lavage fluid (BALF) and transbronchial lung biopsy (TBLB) revealed findings compatible with acute hypersensitivity pneumonitis. We did not consider that the acute hypersensitivity was caused by the patient's Amazon bird, because he had been breeding them for 40 years. However after obtaining a careful history, it became clear that close and frequent contact with the bird had occurred for the first time in the previous year. On the basis of the anti-bird excreta antibody found in the patient's serum and BALF, we diagnosed this case as a case of acute bird fancier's lung caused by the yellow-shouldered Amazon bird. We diagnosed the nodule in right S6 as lung adenocarcinoma by a thoracoscopic lung biopsy, and performed lower lobe lobectomy. We considered that the mediastinal lymph node swellings were caused by hypersensitivity pneumonitis.

Effect of cigarette smoking on the development of murine chronic pigeon breeder's lung. The difference between a short-term and a long-term exposure.

Previous reports suggested that cigarette smoke had a protective effect of on the development of hypersensitivity pneumonitis (HP). However, smoking rate in chronic pigeon breeder's lung (PBL) seemed to be high in our clinical experiences. We developed a murine model of PBL by intranasal instillation with pigeon dropping extracts (PDE) for 4 weeks (short-term exposure) and 17 weeks (long-term exposure) to investigate the effect of cigarette smoke on disease processes. In this model, lung inflammation associated with the production of anti-PDE antibodies and antigen dependent lymphocyte proliferation was induced. Long-term exposure to PDE without cigarette smoking resulted in an increase in lung weight/body weight ratio, total cell number in bronchoalveolar lavage (BAL) fluid, and content of hydroxyproline in the lung compared to shortterm exposure. After a short-term exposure, cigarette smoke lessened the lymphocytosis in BAL fluid, and lymphocyte proliferation. On the other hand, after a long-term exposure cigarette smoke increased lung hydroxyproline. These results suggest that a short-term cigarette smoking attenuates lung inflammation, but a long-term cigarette smoking enhances lung inflammation with fibrosis.

[Three cases of chronic bird fancier's lung associated with the use of feather bedclothes].

We report here 3 cases of chronic bird fancier's lung diagnosed immunologically using antibodies to pigeon dropping extract. None of the patients were bird fanciers but had indirect exposure to birds in their living environment, and had been using feather-filled duvets or pillows for a long time. Two of 3 cases were positive for environmental provocation tests and 2 cases had pathological findings of hypersensitivity pneumonitis such as multinucleated giant cells and non-necrotizing epithelioid cell granulomas. One case was resistant to steroid therapy alone and was successfully treated by coadministration of prednisolone and cyclosporin A. Another case was treated by steroid alone but died of acute exacerbation of unknown cause. These cases suggest that not only feathers but two or more kinds of bird-related antigens were involved in the sensitization immunology and development of bird fancier's disease, and that clinicians should perform thorough history taking with environmental surveillance relevant to birds.

[Bird fancier's lung--an allergic alveolitis]. / Fugleholderlunge--en allergisk alveolitt.

BACKGROUND: Bird fancier's lung is globally the second most frequent cause of extrinsic allergic alveolitis. MATERIAL: For many years, the patient had influenza-like symptoms and developed progressing pulmonary fibrosis. Over a period of 10 years she had been exposed to up to 43 birds in the house at any one time and serum precipitates against avian proteins had been found. After sanitation of the house of birds and avian proteins, the pulmonary function has not deteriorated further in 5 years. INTERPRETATION: A thorough environmental history is essential in the diagnosis of extrinsic allergic alveolitis; at an earlier stage it would have made us think about this possible etiological factor. This could have prevented the development of permanent pulmonary fibrosis if the patient had been advised to avoid further exposure to antigens. There should be greater awareness of this disease among general practitioners as well as among chest consultants in Norway.

Cockatiel-induced hypersensitivity pneumonitis.

Diagnosing an environmental or occupationally related pulmonary disorder often involves a process of elimination. Unlike commonly diagnosed conditions in other specialties, a cause-and-effect relationship may be implied, yet other factors such as temporality and biologic plausibility are lacking. Our patient was referred with a suspected work-related pulmonary disorder. For several years, she had suffered with dyspnea on exertion and repeated flulike illnesses. She worked at an automobile repair garage that performed a large number of emission tests, and there was concern that her workplace exposures were the cause of her symptoms. After a careful review of her history, physical examination, and laboratory testing, we came to the conclusion that she had hypersensitivity pneumonitis related to pet cockatiels in her home. Clinical points of emphasis include the importance of a complete environmental history and careful auscultation of the chest when performing the physical examination. In addition, we encountered an interesting physical diagnostic clue, a respiratory sound that assisted with the eventual diagnosis.

Hypersensitivity pneumonitis associated with home ultrasonic humidifiers.

We describe five patients with hypersensitivity pneumonitis (HP) that was related to using home ultrasonic humidifiers. All patients had micronodular infiltrates on their chest radiograph, and their lung biopsy specimens revealed alveolitis with or without epithelioid cell granulomas. Challenge tests were performed on two patients with the humidifier water and three patients using the humidifier. All patients tested exhibited a positive response. Tests for precipitating antibodies against an extract of the humidifier water gave strongly positive reactions in all patients tested. Precipitins to Cephalosporium acremonium and Candida albicans were also present in all cases, whereas precipitins to thermophilic actinomycetes were not detected. Although cultures of the water grew a variety of fungal and bacterial organisms, thermophilic actinomycetes could not be detected. These findings suggest that thermophilic organisms may not be the causative antigens of HP associated with ultrasonic humidifiers. All five patients had an increase in the bronchoalveolar lavage (BAL) lymphocytes that were predominantly CD4+ lymphocytes. The T helper cell count (CD4) to suppressor T cell count (CD8) ratio was significantly higher than that observed in summer-type HP, and lower than that observed in bird fancier's lung, indicating that the phenotypes of the BAL lymphocytes may vary with the type of HP.

Hypersensitivity pneumonitis due to native birds in a bird ringer.

A bird fancier who had only been exposed to native birds, mostly owls, developed a sever hypersensitivity pneumonitis with a very insidious onset.

Louis E. Siltzbach Memorial Lecture. Concepts of pathogenesis and lung reactivity in hypersensitivity pneumonitis.

It is surprising that forms of hypersensitivity pneumonitis do not occur more frequently, given the variety of biologic dusts and airborne antigens that have been found to cause disease. Exposure is almost universal in some occupations that involve handling animals or feed products, and development of humoral immunity occurs in most; however, overt respiratory illness is relatively infrequent or not easily recognized by the subject. What differs between symptomatic and asymptomatic subjects is not certain, but unique host resistance or susceptibility, as the case may be, appears to be a factor. This may have a genetic basis, but this has not been investigated vigorously. With repeated airborne exposure to appropriate antigens, a humoral and a local respiratory antibody response occur but perhaps with little disease consequence, as most subjects so immunized remain clinically asymptomatic. So far as is known, there is no other route of antigenic exposure except through the respiratory tract, but contact with the antigens could occur on the skin or on mucosal surfaces such as the conjunctiva, or antigens could be ingested by swallowing nasopharyngeal secretions. Except for serum antibodies, however, there is little documentation that other systemic organs are affected, as may occur with sarcoidosis. Of course there is great variability in the age of the subjects and the dosage of antigen to which the subject is exposed, and the frequency and duration of exposure can vary considerably. All of these would seem to be easily tested, however, in an animal model where most of the variables could be independently controlled and varied at will. Even the genetic and aging factors, which are the most difficult parameters to control in humans, could be investigated. Yet, it has been very difficult and perplexing not to have created a more faithful model of hypersensitivity pneumonitis in the laboratory. It is virtually impossible to cause predictable lung disease without the use of an adjuvant that will induce some measure of delayed or cellular hyperreactivity. The acute lung disease caused by antigen-antibody reactions seems too explosive and severe, for its acute disease counterpart of hypersensitivity pneumonitis in humans and the persistence of histologic changes in lung tissue is brief and is usually resolved within 1-2 weeks. A chronic model producing granulomas and fibrosis has been difficult to construct, although the work reported by Fulmer and colleagues is very encouraging.(ABSTRACT TRUNCATED AT 400 WORDS)

A hazard of Christmas: Bird Fancier's Lung and the Christmas tree.

A lady with alveolitis due to her budgerigar developed recurrent symptoms when exposed to allergen left on her artificial Christmas tree.

Time of exposure as a prognostic factor in avian hypersensitivity pneumonitis.

Spirometric values were subsequently evaluated in 22 patients suffering from hypersensitivity pneumonitis caused by avian problems. First spirometric values were abnormal in 18/22 (82%) of patients. A restrictive pattern was observed in 16/22 (72%) of patients and an obstructive pattern in 6/22 (27%). The TLCO was reduced in all cases (12/12). Improvement or normalization of the respiratory function occurred 3.4 +/- 2.4 months after the avian contact had ceased. At the end of the follow-up, parameters were normal in 13/22 (59%) of patients. The restrictive pattern remained unchanged in 7/22 (32%), and the obstructive pattern persisted in 4/22 (18%) of the patients. The TLCO was normal in 6/12 (50%) of patients. Neither age nor treatment with corticosteroids (13 patients) had a significant influence upon the evolution of the lung function. However, total recovery or significant improvement was observed in 12/12 (100%) of patients who had been in contact with birds less than 2 years, in contrast to 6/10 (60%) of patients with more than 2 years of contact (P = 0.002).

Experimental models of hypersensitivity pneumonitis.

Experimental models of hypersensitivity pneumonitis are important tools for the study of the pathogenesis of this disease. In this paper we review the characteristics of the main animal models developed until now. The HP models in rats seem to be particularly appropriate for studying pigeon fancier's disease and the HP induced by chemicals, as well as for studying mediators of acute lesions induced by immunocomplexes. However, the HP models developed in rats are of less value in the evaluation of other aspects of the pathogenesis of this clinical entity in humans. The murine models of HP offer several advantages: the ease and simplicity of intranasal administration, the ability to produce acute and subacute pulmonary lesions similar to those found in humans, the possibility of reproducing lesions similar to those of nonaffected exposed subjects and the possibility of pharmacologically modulating the process. Their disadvantages lie in the different pulmonary lymphocyte response and the difficulty in reproducing a model of chronic fibrosis. The HP models in rabbits are extraordinarily useful for evaluating the immunological mechanisms through which subjects repeatedly exposed to the antigen do not develop clinical manifestations. However, the rabbit has several immunological differences when compared to humans, and the effect of some immunomodulators in this animal is different. The models of HP in guinea-pigs have as advantages the ease in handling the animals, the possibility of pharmacological manipulation, and the ability to induce an acute phase that is very similar to that observed in humans. The drawback, however, is the low lymphocyte response and the striking eosinophilic reaction that contrast with the bronchoalveolar data found in HP in humans. In conclusion, there is no ideal model to reproduce all the findings observed in humans, suggesting that the experimental animal and the method of developing HP should be selected on the basis of concrete research aims.

[Asthmatic child without asthma]. / Een astmatisch kind dat geen astma heeft.

Two boys aged 13 and 7 years, displayed chronic coughing, dyspnoea on exertion, anorexia, weight loss, and fatigue. At first a diagnosis of asthma was made. However, a correct interpretation of anamnestic and clinical features, laboratory findings and radiographic results led to the diagnosis of 'pigeon breeder's disease' in both cases. Both patients recovered after drug treatment and avoidance of re-exposure to pigeon antigen.

[Capability of clinical and laboratory findings to predict the grade of fibrosis and the diagnosis in diffuse interstitial lung diseases]. / Capacidad de clínica y laboratorio para predecir el grado de fibrosis y el diagnóstico en enfermedades pulmonares intersticiales difusas.

Our objective was to assess the capacity of clinical and laboratory information to predict findings in the lung biopsy in interstitial lung diseases (ILD). We studied 121 patients with ILD as a cohort recruited in our institute from 1983 to 1987 with the diagnosis of hypersensitivity pneumonitis (HP) and usual interstitial pneumonia (UIP). Histologic diagnosis (HP vs UIP) and degree of fibrosis (< 50% of the biopsy surface vs > or = 50%) were used as the gold standard to compare a series of clinical and laboratory variables in the initial assessment. We used a stepwise logistic regression model to predict the biopsy results. The model was calculated in half of the patients selected by random sampling, and the calculated model was tested in the other half of the patients. Variables found to predict degree of fibrosis were (with relative risk RR and 95% confidence interval): a radiographic pattern of honeycombing (RR 5.0 from 0.9-29), digital clubbing (RR 8 from 1.4-48) and gender (RR 2.9 from 0.4-20). This model classified correctly 72% of the biopsies, with a sensitivity of 0.38, a specificity of 0.85 and a kappa of 0.25 +/- 0.19 (p = 0.17 NS). For histologic diagnosis (NIU vs NH), the model included gender (RR 6.6, 1.3-33), honeycombing (RR 1.6, from 0.4-6.0), digital clubbing (RR 4.6, from 1.2-18), and vital capacity expressed as percent of predicted (RR 0.96, from 0.92-1.00).(ABSTRACT TRUNCATED AT 250 WORDS)