Inhalation challenge test using pigeon eggs for chronic hypersensitivity pneumonitis.

BACKGROUND: Chronic hypersensitivity pneumonitis (CHP) remains a diagnostic challenge. The process of collecting and extracting serum and droppings from causative animals for the inhalation challenge test is complicated and the risk of inducing disease progression exists. OBJECTIVE: To investigate the utility and safety of an inhalation challenge test using pigeon eggs. METHODS: Pigeon eggs were pasteurized and mixed with a saline solution to produce an inhalation fluid. An inhalation challenge test was conducted on 19 patients with bird-related CHP and 17 patients with interstitial lung disease other than bird-related CHP. To identify antigens in pigeon eggs, the antigen-antibody responses of the pigeon eggs and serum from patients were evaluated using Western blotting. RESULTS: The mean changes in C-reactive protein, alveolar-arterial oxygen difference, erythrocyte sedimentation rate, and lactate dehydrogenase significantly increased by 0.32 mg/dL (P = .014), 7.8 Torr (P = .002), 1.4 mm/h (P = .012), and 5.4 U/mL (P = .0019), respectively, in bird-related CHP group compared to the control 24 hours after the inhalation challenge test. Furthermore, within 24 hours of the inhalation test, the mean forced vital capacity decreased by 2.3% in the bird-related CHP group compared with a decline of 0.05% in the control group (P = .035). Serum collected from seven bird-related CHP patients who underwent the inhalation challenge test and reacted to antigens with molecular weights of 37-75 KDa, and these molecular weights were consistent with egg albumin and globulin. CONCLUSION: Since a mild response was observed after the inhalation challenge test using pigeon eggs, this test was an obvious candidate for diagnosing bird-related CHP.

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

BACKGROUND: Hypersensitivity 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. METHODS: We 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. RESULTS: A 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. CONCLUSIONS: This 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.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Treatment and monitoring of hypersensitivity pneumonitis.

INTRODUCTION: Hypersensitivity pneumonitis (HP) is an immunologically induced lung disease that develops after inhalation of certain environmental antigens only in subjects with susceptibility to antigens. Therefore, both environmental and host immunological factors play important roles in the aetiology and pathogenesis of HP. AREAS COVERED: Determination of an inciting antigen is crucial for diagnosis, treatment and monitoring. For treatment, modification of the environment and of the host immune response are important. The former includes reduction of antigenic burden (i.e. disinfectant, cleaning), protective devices (i.e. filter, respiratory protection mask, ventilation) and avoidance of inciting antigens. The latter includes corticosteroids, lung transplantation and smoking cessation. For monitoring, measurement of serum Krebs von den Lungen (KL)-6 and surfactant protein (SP)-D concentrations can be used to screen for HP and to detect HP activity. Expert commentary: Measurement of an inciting antigen may be useful to predict the progression and prognosis of the disease. Treatment and monitoring are challenging in chronic HP with fibrosis.

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

RATIONALE: 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. OBJECTIVES: 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. METHODS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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.