Chronic Bird-related Hypersensitivity Pneumonitis Research Articles

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.

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.

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.

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.

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.

Utility of immunological tests for bird-related hypersensitivity pneumonitis.

The reaction of specific antibodies and sensitized lymphocytes to antigens is important in hypersensitivity pneumonitis (HP). However, there are no known studies evaluating the utility of the lymphocyte proliferation test (LPT) or specific antibodies to avian antigens in diagnosing bird-related HP. In this study, we examined the sensitivity and specificity of these two tests. Patients with acute bird-related HP (n=10), chronic bird-related HP (n=35), acute summer-type HP (n=14), and other interstitial pneumonia (IP) (n=76) were evaluated. The optimal cutoff values were determined by receiver operating curve (ROC) analyses of specific antibodies in serum and bronchoalveolar lavage fluid (BALF), and by conducting the LPT on mononuclear cells in peripheral blood and BALF. The sensitivity and specificity of the antibodies were 80-100% and 92-100% in acute bird-related HP, and 26-79% and 73-93% in chronic bird-related HP, respectively. The sensitivity and specificity of the LPT were 50-100% and 100% in acute bird-related HP, and 46% and 91% in chronic bird-related HP, respectively. Specific antibodies and the LPT are quite useful for diagnosing acute bird-related HP. The presence of specific antibodies in BALF and the results of LPT with peripheral blood mononuclear cells are particularly useful for diagnosing chronic bird-related HP.

Chronic Bird Related Hypersensitivity Pneumonitis Presenting with Exacerbation due to Use of a Feather Duvet and Improvement after Antigen Avoidance

慢性羽毛ふとん肺は特発性肺線維症と誤診されていることが多い疾患であり，確定診断後は徹底的な抗原回避が重要である．症例は61歳男性．2002年11月より特発性肺線維症として経過観察とされていた．2004年3月当科精査にて慢性羽毛ふとん肺と診断．羽毛布団の使用を中止したが，症状及び検査所見の悪化を認めた．無自覚の抗原曝露を疑いより詳細な問診をしたところ，羽毛布団使用を中止後も自宅の押入れの中に保管していため抗原曝露は継続していたと考えられた．破棄により，症状・検査所見の改善を認めた．