Bird-related Hypersensitivity Pneumonitis Research Articles

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

BackgroundBird-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. MethodsOf 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. ResultsIn 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. ConclusionsBird-specific IgG antibody with ImmunoCAP® was useful for screening and diagnosing BRHP caused by other bird species and duvets.

Development of a new HISCL automated CXCL9 immunoassay

C–X–C motif chemokine ligand 9 (CXCL9), a candidate biomarker, reflects type 1 (T1) inflammation pathology. Here, we report the analytical performance and clinical characteristics of a new CXCL9 reagent for a fully automated immunoassay device. We evaluated the limits of blank, detection, and quantitation (LoQ) along with other efficacy parameters, and the ability of the assay to report patient health, COVID-19 status, and the presence of asthma and/or interstitial lung diseases (ILDs). The coefficient of variation for 5-day total precision using two instruments was 7% across two controls, serum, and plasma panels. LoQ of 2.2 pg/mL suggested the efficacy of the assay in detecting T1 inflammation in plasma or serum; no cross-reactivity or interference was observed. We identified high serum CXCL9 levels in samples from patients with acute COVID-19 infections (n = 57), chronic bird-related hypersensitivity pneumonitis (n = 61), asthma (n = 194), and ILDs (n = 84) compared to healthy individuals (< 39.0 pg/mL). Furthermore, CXCL9 levels increased with age in asthma patients, and an opposite trend was observed for T2 inflammatory factors. These results suggest the utility of the automated CXCL9 immunoassay for measuring CXCL9 in clinical samples and reflect its role in T1 inflammation.

Immunopathological Mechanisms of Bird-Related Hypersensitivity Pneumonitis.

Bird-related hypersensitivity pneumonitis (BRHP) is an interstitial lung disease induced by avian proteins. The immunopathological pathways involved in the disease are still unknown. This study assesses the cellular immune response and the cytokine pattern in a mouse model of BRHP. On days -3 and -1, mice were intraperitoneally sensitized with commercial pigeon serum (PS) or saline. Intranasal instillations with PS or saline were carried out on three consecutive days/week over either 3 weeks (Group 1) or 12 weeks (Group 2). Leukocyte and cytokine patterns in lung tissue and pulmonary inflammation in bronchoalveolar lavage (BAL) were analysed. Both groups presented increases in resident monocytes, interstitial macrophages and type 2 dendritic cells (DCs), but also reductions in inflammatory monocytes, alveolar macrophages and tolerogenic DCs compared with their control groups. Group 1 had increased levels of eosinophils and T cells with reductions in neutrophils and B cells, while Group 2 showed high levels of B cells. Both groups exhibited increases in Th1 and Th2 cytokines. Group 2 also showed increased levels of IL-23, a Th17 cytokine. Increased levels of neutrophils, eosinophils and lymphocytes were observed in BAL samples of both groups compared with controls. In the first stages of BRHP, there is a mixed Th1/Th2 immune response, while during the progression of the disease, although there is a Th1 response, the cytokine levels seem to indicate a switch towards a Th2/Th17 mixed response.

Serum Immunoglobulin G Testing against Pigeon Egg in Stable Fibrotic Hypersensitivity Pneumonitis

Introduction: The accuracy of serum immunoglobulin (Ig) G testing for diagnosis of stable bird-related fibrotic hypersensitivity pneumonitis (HP) is controversial. Furthermore, avian serum, extracts, or feathers were employed as antigens in bird-related HP; however, the usage of egg whites has not been reported. We investigated the utility of IgG testing against pigeon egg whites in patients with stable bird-related fibrotic HP. Methods: Patients having a positive inhalation test for pigeon antigen and a histological investigation with diagnostic confidence of fibrotic HP greater than moderate confidence were included. The control group consisted of patients with interstitial lung diseases (ILDs) other than HP. To select patients in the stable phase, patients with fibrotic HP were excluded if they were clinically considered to be in the acute exacerbation or acute phase. The IgG testing against pigeon egg whites by enzyme-linked immunosorbent assay and the commercialized anti-pigeon IgG testing by fluorescence enzyme immunoassay were investigated. Results: In this study, 37 patients with stable bird-related fibrotic HP and 32 patients with ILDs other than HP participated. Serum IgG testing for pigeon egg whites revealed that the control group’s optical density was 0.147 and the group with bird-related fibrotic HP had a mean value of 0.207 (p = 0.011). IgG testing in bronchial alveolar lavage fluid was not significantly higher in the bird-related fibrotic HP group than in controls (p = 0.42). No significant difference in area under the curve between an IgG testing against pigeon egg whites and a commercialized anti-pigeon IgG testing was observed (p = 0.24). Test accuracy for stable bird-related fibrotic HP ranged from 62% to 76% sensitivity and 59–66% specificity. Conclusion: IgG testing to identify the inciting antigen in patients with stable bird-related fibrotic HP had relatively low accuracy.

Validation of inhalation challenge test and serum immunoglobulin G test for bird-related fibrotic hypersensitivity pneumonitis

BackgroundThe inhalation challenge test is considered to be the item for diagnosis of hypersensitivity pneumonitis (HP) and identifying the causative antigen in patients with fibrotic HP. However, the inhalation challenge test is not widely used. ObjectiveTo evaluate the values of the inhalation challenge test by comparing with serum immunoglobulin (Ig)G test. MethodsThis was a single-center, retrospective study. The patients with fibrotic HP were diagnosed pathologically by surgical lung biopsy or transbronchial lung cryobiopsy and were assumed to have bird-related fibrotic HP if they had a history of obvious avian exposure. ResultsOn the basis of pathologic findings and history of avian exposure, 43 of 86 patients were diagnosed with having bird-related fibrotic HP. In 43 patients with bird-related fibrotic HP, 15 (35%) were positive for anti-bird IgG antibody and 36 (84%) were positive for the inhalation challenge test; in addition, the specificity of the inhalation challenge test was 67%. Patients with both positive results from inhalation challenge test and anti-bird IgG antibodies had a 2.7% decline in annual forced vital capacity (FVC) before the inhalation (P = .02). In patients with positive result from inhalation challenge test and negative result from anti-bird IgG antibodies, the annual FVC decreased by 5.8% (P = .03). FVC was not consistent in patients with positive result from the anti-bird IgG antibodies. ConclusionThe inhalation challenge test for bird-related fibrotic HP was more sensitive than the anti-bird IgG antibodies. Furthermore, the inhalation challenge test could select patients with similar disease progression.

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

BackgroundThe 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 presentationA 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.ConclusionWe 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.

Screening and diagnosis of acute and chronic bird-related hypersensitivity pneumonitis by serum IgG and IgA antibodies to bird antigens with ImmunoCAP®

BackgroundBird antigens are some of the most relevant antigens in hypersensitivity pneumonitis (HP). Possible sources of bird antigens are bird breeding, feather products and fertilizer with fowl droppings. For the screening and diagnosis of HP, the measurement of bird-specific antibodies should be standardized. The aim of this study was to clarify the utility of serum IgG (sIgG) and IgA (sIgA) antibodies to bird antigens in screening and diagnosing acute/chronic bird-related HP with ImmunoCAP® in multi-centre clinical research. MethodsWe executed a clinical performance test by conducting a multi-institutional study to measure the levels of sIgG/sIgA against pigeon, parrot and budgerigar antigens by the ImmunoCAP® system in 29 acute and 46 chronic bird-related HP patients. ResultsThe levels of sIgG/sIgA against the bird antigens of the three species were significantly higher in subjects with acute bird-related HP and chronic bird-related HP with acute episodes (recurrent type) than in the control subjects. For sIgG, the optimal cutoff values by receiver operating characteristic (ROC) analysis were 24.6 mgA/L for pigeon, 14.0 mgA/L for parrot, and 8.7 mgA/L for budgerigar. By measuring multiple bird antigens and combining sIgG values of two species, the sensitivity and specificity for acute and recurrent-type chronic bird-related HP patients were 85–91% and 73–80%, respectively. For recurrent and insidious types of chronic bird-related HP, the sensitivity and specificity were 48–61% and 73–80%, respectively. ConclusionsMeasurement of the levels of sIgG/sIgA against pigeon, budgerigar and parrot antigens by ImmunoCAP® was useful for screening and diagnosis in bird-related HP.

Changes in serum KL-6 levels during short-term strict antigen avoidance are associated with the prognosis of patients with fibrotic hypersensitivity pneumonitis caused by avian antigens

Bird-related hypersensitivity pneumonitis (BRHP) is the most common type of fibrotic hypersensitivity pneumonitis (HP). Antigen avoidance (AA) is a key step in the diagnosis and management of HP, but not all fibrotic HP patients improve through AA. Because of the poor prognosis of fibrotic HP, predictive biomarkers to identify patients showing rapid progression during AA are urgently needed. From a retrospective review of the medical records of 1941 patients with interstitial lung disease, 75 cases of fibrotic BRHP confirmed by a provocation test or surgical lung biopsy were identified. To identify potential prognostic markers obtained at or around diagnosis, physiological and serological variables at diagnosis and the relative changes in those variables during strict AA were evaluated. Cox proportional hazards models with log-rank testing were used to compare the associations between these variables and survival. Univariate analyses showed that gender, smoking status, and the relative change in the serum levels of Krebs von den Lungen-6 (KL-6) were associated with prognosis (P=0.02, 0.04, and 0.02, respectively), but the presence of honeycombing and the forced vital capacity were not associated with survival. The relative change in KL-6 levels (greater than vs. less than a 10% decrease) was significantly associated with survival in a stratified analysis (73.9 vs. 34.9 months; P=0.04). The relative change in KL-6 levels is associated with the prognosis of patients with fibrotic BRHP independent of previously identified prognostic biomarkers. This finding could help pulmonologists identify fibrotic BRHP patients that are likely to show rapid progression.

【特集】日本人が見つけた自己抗原・抗原 過敏性肺炎の原因抗原：夏型過敏性肺炎の原因抗原特定に至るまでの経緯と鳥関連過敏性肺炎の抗原同定の試み

【特集】日本人が見つけた自己抗原・抗原 過敏性肺炎の原因抗原：夏型過敏性肺炎の原因抗原特定に至るまでの経緯と鳥関連過敏性肺炎の抗原同定の試み

A Case Report of Patient with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis During the Course of Chronic Bird-related Hypersensitivity Pneumonitis.

A Case Report of Patient with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis During the Course of Chronic Bird-related Hypersensitivity Pneumonitis.

Serum CXCL9 and CCL17 as biomarkers of declining pulmonary function in chronic bird-related hypersensitivity pneumonitis

The clinical course of chronic hypersensitivity pneumonitis (HP) with fibrosis is similar to that of idiopathic pulmonary fibrosis (IPF). Current research is expected to identify biomarkers effective in predicting the deterioration of lung function in a clinical setting. Our group analyzed the relationships between the following parameters in chronic bird-related HP: patient characteristics, serum markers, lung function, HRCT findings, BALF profiles, and the worsening of lung function. We also analyzed serum levels of CXCL9, CCL17, and Krebs von den Lungen 6 (KL-6) as serum markers. Patients showing declines in vital capacity (VC) of over 5% at 6 months after first admission were categorized as the “decline group”; the others were categorized as the “stable group.” The serum level of CCL17 and the percentage of BALF macrophages were significantly higher in the decline group compared to the stable group. Serum levels of CXCL9 and CCL17 were significant variables in a multivariate logistic regression analysis of factors associated with VC decline. Patients with a chemokine profile combining lower serum CXCL9 and higher serum CCL17 exhibited significantly larger VC decline in a cluster analysis. Higher serum CCL17 and lower serum CXCL9 were important predictors of worsening lung function in patients with chronic bird-related HP.

Periostin as a predictor of prognosis in chronic bird-related hypersensitivity pneumonitis

BackgroundPeriostin is an established biomarker of Th2 immune response and fibrogenesis. Recent research has indicated that periostin plays an important role in the pathogenesis of idiopathic interstitial pneumonias. To clarify the relationship between periostin and pathogenesis in chronic bird-related hypersensitivity pneumonitis (HP) and to reveal the usefulness of serum periostin levels in diagnosing and managing chronic bird-related HP. MethodsWe measured serum periostin in 63 patients with chronic bird-related HP, 13 patients with idiopathic pulmonary fibrosis, and 113 healthy volunteers. We investigated the relationship between serum periostin and clinical parameters, and evaluated if the baseline serum periostin could predict the prognosis. ResultsSerum periostin was significantly higher in patients with chronic bird-related HP compared to the healthy volunteers. In chronic bird-related HP, serum periostin had significant positive correlations with serum KL-6 levels, the CD4/CD8 ratio in bronchoalveolar lavage fluid, and fibrosis score on HRCT, and a significant negative correlation with the diffusing capacity of the lungs for carbon monoxide. Chronic bird-related HP patients with serum periostin levels exceeding ≥92.5 ng/mL and ≥89.5 ng/mL had a significantly worse prognosis and significantly higher frequency of acute exacerbation, respectively. Higher serum periostin (92.5 ng/mL or higher; binary response for serum periostin) was an independent prognostic factor in multivariate analysis. ConclusionsSerum periostin may reflect the extent of lung fibrosis and play an important role in pathogenesis of chronic bird-related HP. Elevated serum periostin could be a predictor of prognosis in patients with chronic bird-related HP.

Acute inflammatory and immunologic responses against antigen in chronic bird-related hypersensitivity pneumonitis

BackgroundHypersensitivity pneumonitis (HP) is an immune-mediated lung disease induced by the inhalation of a wide variety of antigens and a persistent antigen exposure induces inevitably pulmonary fibrosis in chronic HP. Although neutrophils, Th1 and Th17 cells contribute to lung inflammation in acute phase of HP, there is no clear explanation as to how the immunological reaction occurs just after the inhalation of causative antigens in the chronic phase of HP. MethodsWe examined the inflammatory and immunologic profiles before and after the inhalation provocation test (IPT) in serum and bronchoalveolar lavage fluid (BALF) from patients with chronic bird-related HP (BRHP) and other interstitial lung diseases (ILDs). We analyzed BALF samples from 39 patients (19 BRHP and 20 other ILDs) and serum samples from 25 consecutive patients (20 BRHP and 5 other ILDs) who underwent the IPT. ResultsA significant increase of neutrophils was observed in the BALF from the BRHP patients following the IPT. Neutrophil chemoattractants, namely, granulocyte colony-stimulating factor, IL-6, IL-8, IL-17, and CXCL2 significantly increased in both the serum and BALF of the BRHP patients after the IPT. Serum IFN-γ and CXCL10, cytokines/chemokines that contributed to Th1 inflammation, were also significantly increased in BRHP following the IPT. ConclusionsThis study demonstrated the exposure to the causative antigen provoked acute neutrophilic and Th1 immunologic responses similar to acute HP even in the chronic phase of HP.

Histological variability and consequences in chronic bird-related hypersensitivity pneumonitis.

Lobar and temporal histological variability in chronic bird-related hypersensitivity pneumonitis (BRHP) has not been clearly elucidated. This study was designed to evaluate the spatio-temporal histopathological variability in chronic BRHP. Fifty-two patients with chronic BRHP who underwent a surgical lung biopsy (SLB) between 1992 and 2008 were evaluated. The histopathological characteristics of the lung biopsy specimens were classified by the 2002 American Thoracic Society/European Respiratory Society (ATS/ERS) consensus classification of idiopathic interstitial pneumonias (IIPs). Autopsy specimens from seven patients were also evaluated to examine the serial changes from SLB to autopsy. In a study of lobar histological variability based on the findings of SLB, 7 patients were diagnosed with cellular nonspecific interstitial pneumonia (NSIP) pattern, 16 with fibrotic NSIP pattern, 20 with fibrotic NSIP pattern and usual interstitial pneumonia (UIP) (discordant UIP) pattern and 9 with UIP (concordant UIP) pattern. In a study of sequential changes, specimens of SLBs with fibrotic NSIP pattern changed to a bronchiolocentric interstitial pneumonia (BIP) pattern or UIP pattern. Interlobar and intralobar histological variability is present in chronic BRHP. In several patients with chronic BRHP, a fibrotic NSIP pattern may be an early lesion that progresses to a UIP pattern.

Protein antigen of bird-related hypersensitivity pneumonitis in pigeon serum and dropping

BackgroundAvian antigen is a common cause of hypersensitivity pneumonitis (HP). Inhalation challenge with pigeon serum and pigeon dropping extract (PDE) elicits a hypersensitivity reaction in patients with bird-related hypersensitivity pneumonitis (BRHP), but the antigenic components in these materials have yet to be fully elucidated.MethodPigeon serum, pigeon intestine homogenates, and PDE were immunoblotted with serum samples from 8 patients with BRHP, 2 patients with summer-type HP, 2 patients with humidifier lung, and 3 healthy volunteers. Among the protein spots found in both pigeon serum and PDE, those that reacted with sera from BRHP patients were identified by mass spectrometry. Immunoassays using recombinant protein were performed to confirm the antigenicity of the identified protein. Cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with recombinant protein was also assessed.ResultsImmunoglobulin lambda-like polypeptide-1 (IGLL-1) was identified from all spots on 2-DE immunoblots of both pigeon serum and PDE. The BRHP patients exhibited higher levels of serum IgG antibody against the recombinant IGLL-1 (rIGLL-1) compared to the control subjects, as well as a stronger PBMCs proliferative response to rIGLL-1. Cytokine production by PBMCs from BRHP patients after rIGLL-1 exposure indicated that the protein could induce Th1 prone immune responses: an increase in TNF-α and an absence of elevated IL-10 production.ConclusionsPigeon IGLL-1 was identified as the BRHP antigen present in both pigeon serum and PDE.

Factors associated with positive inhalation provocation test results in subjects suspected of having chronic bird-related hypersensitivity pneumonitis.

Chronic bird-related hypersensitivity pneumonitis (BRHP) is often misdiagnosed as other interstitial lung diseases. While the utility of the inhalation provocation test (IPT) has been reported, the test is not commonly performed. In this study, we aimed to identify significant clinical variables associated with positive inhalation provocation test results in subjects suspected of having chronic BRHP. This would help clinicians decide whether to perform IPT in patients suspected of having chronic BRHP in real-life practice. We retrospectively evaluated 107 patients who underwent the IPT for suspected chronic BRHP. We used the IPT as the gold standard diagnostic tool for chronic BRHP. Specific antibodies against pigeon dropping extract were documented in 52% of the IPT-positive patients but also in 38% of the IPT-negative patients (p=0.172). By using the logistic regression model, three significant predictors of IPT results were identified as follows: (1) a history of raising birds (odds ratio [OR] 3.112), (2) exposure to birds from the surrounding environment (OR 7.321), (3) white blood cell count (×102/μl; OR 0.959). This study demonstrates that current or past exposure to avian antigens is a positive predictor of positive IPT results in patients suspected of having chronic BRHP.

Chronic Hypersensitivity Pneumonitis With a Usual Interstitial Pneumonia-Like Pattern: Correlation Between Histopathologic and Clinical Findings

Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by the inhalation of environmental antigens. The relationship between clinical, radiologic, and histopathologic findings of chronic HP remains unclear. Sixteen patients with proven chronic bird-related HP with a usual interstitial pneumonia-like pattern were analyzed retrospectively. Histopathologic findings were semiquantitatively assessed and compared with clinical and radiologic findings. We also evaluated the histopathologic findings affecting prognosis. The extent of centrilobular fibrosis was negatively correlated with Pao2 (r= -0.55, P= .03). The extent of bridging fibrosis was positively correlated with the ratio of maximal expiratory flow at 50%of forced vital capacity to that at 25%(r= 0.60, P= .02). Patients with a greater extent of fibroblastic foci (FF) had more radiologic reticulation (P= .01), honeycombing (P= .01), and traction bronchiectasis (P= .02), and had significantly shorter survival time (P= .01) than patients with a lesser extent of FF. Multivariate analysis showed that the extent of FF was a significant prognostic factor (hazard ratio, 2.36; 95%confidence interval, 1.02-5.48; P= .04). Our findings demonstrated that the extent of FF was significantly associated with reticulation, honeycombing, and traction bronchiectasis on high-resolution CT scanning. Moreover, the extent of FF could be a useful predictor of mortality in chronic HP with a usual interstitial pneumonia-like pattern.

Interleukin-17A and Neutrophils in a Murine Model of Bird-Related Hypersensitivity Pneumonitis.

Hypersensitivity pneumonitis (HP) is an immune mediated lung disease induced by the repeated inhalation of a wide variety of antigens. Bird-related hypersensitivity pneumonitis (BRHP) is one of the most common forms of HP in human and results from the inhalation of avian antigens. The findings of a recent clinical analysis suggest that in addition to Th1 factors, the levels of interleukin(IL)-17 and IL-17-associated transcripts are increased in the setting of HP, and that both IL-17A and neutrophils are crucial for the development of pulmonary inflammation in murine models of HP. Our objectives were to investigate the roles of IL-17A and neutrophils in granuloma-forming inflammation in an acute HP model. We developed a mouse model of acute BRHP using pigeon dropping extract. We evaluated the process of granuloma formation and the roles of both IL-17A and neutrophils in a model. We found that the neutralization of IL-17A by the antibody attenuated granuloma formation and the recruitment of neutrophils, and also decreased the expression level of chemokine(C-X-C motif) ligand 5 (CXCL5) in the acute HP model. We confirmed that most of the neutrophils in the acute HP model exhibited immunoreactivity to the anti-IL-17 antibody. We have identified the central roles of both IL-17A and neutrophils in the pathogenesis of granuloma formation in acute HP. We have also assumed that neutrophils are an important source of IL-17A in an acute HP model, and that the IL-17A-CXCL5 pathway may be responsible for the recruitment of neutrophils.

The amount of avian antigen in household dust predicts the prognosis of chronic bird-related hypersensitivity pneumonitis.

Bird-related hypersensitivity pneumonitis is induced by inhalation of avian antigen. Evaluation to avoid repeated exposure to avian antigen is a key part of the treatment for bird-related hypersensitivity pneumonitis. It can be difficult, however, to reliably evaluate exposure to the antigen because bird-related hypersensitivity pneumonitis in its chronic form may be caused by unrecognized and indirect exposure. The purpose of the present study is to establish a method for measuring environmental avian antigen in patients with chronic bird-related hypersensitivity pneumonitis and to evaluate the clinical utility of the method. The amount of avian antigen was measured in samples of dust collected from the household environments of patients with chronic bird-related hypersensitivity pneumonitis. The patients whose clinical progress could be followed by periodic pulmonary function tests for 1 year were classified into a deterioration group and a stable group. Age, sex, smoking status, FVC % predicted, and the amount of avian antigen in household dust samples at the diagnosis of bird-related hypersensitivity pneumonitis, as well as survival, were determined and evaluated for each group. The total number of subjects was 23. The clinical condition deteriorated in 11 patients and remained stable in 12. The amount of avian antigen in household dust samples was significantly higher for the deterioration group than for the stable group. In logistic regression analysis, avian antigen was the only variable found to be significant for distinguishing between the two groups. The patients with higher amounts household dust avian antigen had a poor prognosis in the survival analysis. Avian antigen was the only variable to significantly influence the prognosis of chronic bird-related hypersensitivity pneumonitis. The levels of exposure to avian antigen were related to disease progression and prognosis in chronic bird-related hypersensitivity pneumonitis.

Validation of inhalation provocation test in chronic bird-related hypersensitivity pneumonitis and new prediction score.

Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease induced by the inhalation of any of a wide variety of antigens. For example, bird-related HP (BRHP) results from the inhalation of avian antigens. The clinical features of chronic HP, including imaging and histological findings, are similar to those of idiopathic pulmonary fibrosis. Despite its status as the "gold standard," the inhalation provocation test (IPT) is rarely performed, because the methods and the criteria are not standardized. In 2000, we reported the utility of IPT for pigeon dropping extracts. The purpose of the current study was to validate the utility and safety of the test, and to differentiate chronic HP from other interstitial lung diseases. A total of 28 patients with chronic BRHP and 19 control subjects were evaluated in this retrospective study. We validated the previous criteria and proposed new criteria using prediction scores. In the IPT using pigeon dropping extracts, the previous criteria showed a sensitivity of 78.6% and a specificity of 94.7% in this retrospective study. The increases in the peripheral white blood cell count and C-reactive protein levels are good indicators of a positive response to the inhalation challenge. We propose the use of the IPT prediction score (∆WBC [%] + 2 × ∆P[a - a]O2 [mm Hg], where WBC is white blood cell) and the prediction rule, which showed high sensitivity and specificity values of 92.9 and 94.7%, respectively. Two (1.5%) out of a total of 130 subjects who underwent the tests required treatment after the challenge. The IPT is a useful and safe tool for the diagnosis of chronic HP. The IPT prediction score that we have proposed has high sensitivity and specificity in the diagnosis of chronic BRHP.