Tomoya Tateishi

Clinical Predictors and Histologic Appearance of Acute Exacerbations in Chronic Hypersensitivity Pneumonitis

BACKGROUND Acute exacerbations (AEs) in idiopathic pulmonary fibrosis (IPF) are critical factors for its clinical course and prognosis. We have seen AEs and poor prognosis consequent to AE in patients with chronic hypersensitivity pneumonitis (HP), as has been seen in patients with IPF. The aim of this study was to evaluate the clinical features of the patients with AE in those with chronic HP. METHODS We reviewed 100 consecutive patients with chronic bird fancier lung (BFL) from 1993 to 2006, and analyzed the clinical characteristics, including history, and laboratory and immunologic, imaging, BAL, and histologic findings. RESULTS AE developed in 14 patients during this observation period (AE group), whereas 86 patients remained stable (non-AE [NAE] group). The 2-year frequency of AE among patients with chronic BFL having usual interstitial pneumonia (UIP)-like lesions seen on surgical lung specimens was 11.5%. Patients with AE were more likely to be smokers (p = 0.003). In pulmonary function test results, the mean total lung capacity (TLC) and diffusing capacity of the lung for carbon monoxide (Dlco) were lower in patients with AEs (TLC: AE patients, 63.0 +/- 16.8%; NAE patients, 81.6 +/- 20.0%; Dlco: AE patients, 41.9 +/- 19.0%; NAE patients, 60.0 +/- 19.4%). The mean number of lymphocytes in BAL fluid were lower (AE patients, 13.7 +/- 7.5 lymphocytes; NAE patients, 37.2 +/- 29.7 lymphocytes), while the number of neutrophils were greater in AE patients (AE patients, 10.7 +/- 17.6 neutrophils; NAE patients, 3.6 +/- 4.4 neutrophils). Histologic and/or radiologic findings revealed that all AE patients had UIP-like lesions. Diffuse alveolar damage was observed in six cases, whereas organizing pneumonia superimposed on preexistent fibrotic lesions was observed in two cases. CONCLUSIONS The present study showed several predictive factors for AE at the time of diagnosis. Low TLC and Dlco, low lymphocyte levels in BAL fluid, and a UIP-like pattern in histology at the time of diagnosis may be the risk factors for AE.

Serial high-resolution computed tomography findings of acute and chronic hypersensitivity pneumonitis induced by avian antigen.

Purpose: The purpose of this study was to evaluate serial changes and the prognostic value of high-resolution computed tomographic (HRCT) findings in hypersensitivity pneumonitis (HP). Method: The medical records of 112 patients with bird-related HP (17 acute, 33 recurrent, and 62 insidious) were retrospectively reviewed. High-resolution computed tomographic findings at the time of diagnosis and at follow-up were retrospectively interpreted. Results: Ground-glass opacities and centrilobular nodules were predominant findings in acute and recurrent HP, whereas honeycombing was the outstanding feature in insidious HP. Areas of ground-glass opacities and centrilobular nodules decreased in all groups over a long-term follow-up. Areas of honeycombing, on the other hand, increased in chronic HP, especially in the insidious cases. Cox regression models revealed a higher mortality risk in cases with airspace consolidation and honeycombing on HRCT. Conclusion: Acute, recurrent, and insidious HP all have characteristic features on CT. Characteristic HRCT findings can predict the prognosis of chronic HP.

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.

Antigen avoidance tests for diagnosis of chronic hypersensitivity pneumonitis

BACKGROUND Chronic hypersensitivity pneumonitis (HP) is induced by the inhalation of specific antigens. Patients with chronic HP may be able to improve their prognosis by avoiding these antigens. Chronic HP is often difficult to distinguish from idiopathic interstitial pneumonias (IIPs). OBJECTIVE This study was performed to find out how antigen avoidance tests contribute to the diagnosis of chronic HP. METHODS A retrospective analysis was conducted on 265 patients who underwent 2-week antigen avoidance tests between April 2002 and March 2012. The patients were classified into the following categories: acute HP, chronic HP, collagen vascular disease-associated interstitial pneumonia (CVD-IP), lung dominant connective tissue disease (LD-CTD), and IIPs. The following seven clinical parameters were evaluated: vital capacity, alveolar-arterial oxygen pressure difference, Krebs von den Lungen-6, surfactant protein-D, white blood cell count, C-reactive protein, and body temperature. These parameters were compared between the chronic HP group and a control group consisting of CVD-IP, LD-CTD, and IIPs. RESULTS One-hundred and ninety-six patients with chronic HP and 43 control subjects were evaluated. All clinical parameters improved significantly in the chronic HP group but showed no significant changes in the control group. Four of the parameters changed significantly compared with the control group. Diagnostic criteria established using these data had a sensitivity of 51.0% and a specificity of 80.7%. CONCLUSIONS It was difficult to diagnose chronic HP based solely on 2-week antigen avoidance tests; however, improved clinical parameters among patients supported the diagnosis 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.