Project description:Despite well-documented case series of hypersensitivity pneumonitis (HP), epidemiological data delineating relative contributions of risk factors are sparse. To address this, we estimated HP risk in a case-referent study of occupational and nonoccupational exposures. We recruited cases of HP by ICD-9 codes from an integrated healthcare delivery system (IHCDS) and a tertiary medical care centre. We drew referents, matched for age and sex, from the IHCDS. Participants underwent comprehensive, structured telephone interviews eliciting details of occupational and home environmental exposures. We employed a hierarchical analytic approach for data reduction based on the false discovery rate method within clusters of exposures. We measured lung function and selected biomarkers in a subset of participants. We used multivariate logistic regression to estimate exposure-associated odds ratios (ORs) and population attributable fractions (PAFs) for HP. We analysed data for 192 HP cases (148 IHCDS; 44 tertiary care) and 229 referents. Occupational exposures combined more than doubled the odds of developing HP (OR 2.67; 95% CI 1.73-4.14) with a PAF of 34% (95% CI 21-46%); nonoccupational bird exposure also doubled the HP odds (OR 2.02; 95% CI 1.13-3.60), with a PAF of 12% (3-21%). Lung function and selected biomarkers did not substantively modify the risk estimates on the basis of questionnaire data alone. In a case-referent approach evaluating HP risk, identifiable exposures accounted, on an epidemiological basis, for approximately two in three cases of disease; conversely, for one in three, the risk factors for disease remained elusive.
Project description:BackgroundVariable clinical courses make it challenging to predict mortality resulting from fibrotic hypersensitivity pneumonitis (HP). This study evaluated the usefulness of radiologic parameters for predicting mortality in patients with fibrotic HP.MethodsClinical data and high-resolution computed tomography (HRCT) images, which were scored for reticulation, honeycombing, ground glass opacity (GGO), consolidation, and mosaic attenuation (MA) by visual assessment, were retrospectively analyzed in a total of 101 patients with fibrotic HP (all biopsy-proven cases). Fibrosis score was defined as the sum of reticulation and honeycombing scores.ResultsThe mean age of the 101 patients was 58.9 years, and 60.4% were females. During the follow-up (median: 55.5 months; interquartile range: 37.7-89.0 months), the 1-, 3-and 5-year mortality rates were 3.9, 16.8, and 32.7%, respectively. The non-survivors were older and had significantly lower lung function and minimum oxygen saturation during the 6-min walk test than the survivors. The non-survivors had higher scores of reticulation, honeycombing, GGO, fibrosis, and MA on HRCT than survivors. In the multivariable Cox analysis, reticulation, GGO, and fibrosis scores were independent prognostic factors for mortality in patients with fibrotic HP, as well as age. Fibrosis score showed great performance for predicting the 5-year mortality (AUC = 0.752, p < 0.001) and higher mortality was recorded for patients with high fibrosis score (≥12.0%) (the mean survival time: 58.3 vs. 146.7 months, p < 0.01) than those without.ConclusionOur results suggest that radiologic fibrosis score may be a useful predictor of mortality in patients with fibrotic HP.
Project description:BACKGROUND:Chronic hypersensitivity pneumonitis (CHP) is a fibrotic parenchymal lung disease that occurs when inhalation of environmental antigens leads to immune dysregulation. Autoimmune features have recently been identified as potentially important among patients with CHP. However, the relationship between hypothyroidism (HT) and CHP is unknown. In this study, we investigate the prevalence and impact of HT among patients with CHP. METHODS:We conducted a retrospective, case-control analysis. We identified 121 patients at the University of Chicago Interstitial Lung Disease Center with a multidisciplinary diagnosis of CHP. These patients were matched 3:1 according to age, sex, and race to 363 control subjects with asthma from 2006 to 2015. We analyzed demographics, clinical characteristics, and survival between both groups and assessed the relationship of HT with CHP. Survival analysis was performed using Cox proportional hazards modeling. RESULTS:Patients with CHP had higher prevalence of HT (25.6%, n?=?31) compared to controls (10.7%, n?=?39; OR, 2.86; 95% CI, 1.62-4.99; P?<?0.0001). Compared to CHP alone, patients with CHP/HT were more likely to be female (80.6 vs 51.1%, P?=?0.004), have increased incidence of autoimmune disease (19.4 vs 3.3%, P?=?0.009), antinuclear antibody seropositivity (80.6 vs 57.0%, P?=?0.019), and higher TSH levels (4.0 vs 1.9?mIU/L, P?<?0.0001). HT was a significant independent predictor of mortality among CHP patients with seropositive ANA (HR, 3.39; 95% CI, 1.31-8.80; P?=?0.012). CONCLUSION:HT is common in patients with CHP and may carry prognostic significance in patients with features of autoimmunity. Further research exploring common pathogenic pathways between autoimmune HT and CHP may illuminate the association of HT with survival.
Project description:BackgroundHypersensitivity pneumonitis (HP) is an inhaled antigen-mediated interstitial lung disease (ILD). Advanced disease may necessitate the need for lung transplantation. There are no published studies addressing lung transplant outcomes in HP. We characterized HP outcomes compared with referents undergoing lung transplantation for idiopathic pulmonary fibrosis (IPF).MethodsTo identify HP cases, we reviewed records for all ILD lung transplantation cases at our institution from 2000 to 2013. We compared clinical characteristics, survival, and acute and chronic rejection for lung transplant recipients with HP to referents with IPF. We also reviewed diagnoses of HP discovered only by explant pathology and looked for evidence of recurrent HP after transplant. Survival was compared using Kaplan-Meier methods and Cox proportional hazard modeling.ResultsWe analyzed 31 subjects with HP and 91 with IPF among 183 cases undergoing lung transplantation for ILD. Survival at 1, 3, and 5 years after lung transplant in HP compared with IPF was 96%, 89%, and 89% vs 86%, 67%, and 49%, respectively. Subjects with HP manifested a reduced adjusted risk for death compared with subjects with IPF (hazard ratio, 0.25; 95% CI, 0.08-0.74; P = .013). Of the 31 cases, the diagnosis of HP was unexpectedly made at explant in five (16%). Two subjects developed recurrent HP in their allografts.ConclusionsOverall, subjects with HP have excellent medium-term survival after lung transplantation and, relative to IPF, a reduced risk for death. HP may be initially discovered only by review of the explant pathology. Notably, HP may recur in the allograft.
Project description:Background and objectiveA proportion of patients with fibrotic hypersensitivity pneumonitis (fHP) follow a progressive disease course despite immunosuppressive treatment. Little is known about predictors of mortality in fHP. We aimed to investigate the impact of short-term lung function changes in fHP on mortality.MethodsBaseline demographics for 145 consecutive patients with a multi-disciplinary team diagnosis of fHP, as well as baseline and 1-year follow-up of lung function, baseline echocardiographic findings, bronchoalveolar lavage (BAL) cellularity and all-cause mortality were recorded. Changes in forced vital capacity (FVC) ≥ 5% and ≥10%, and diffusion capacity of the lung for carbon monoxide (DLCO) ≥ 10% and ≥15% at 1 year were calculated. Cox proportional hazards analysis was performed to test for associations with mortality.ResultsBaseline lung function severity, age, presence of honeycombing on computed tomography (CT) and echocardiographic pulmonary arterial systolic pressure (PASP) ≥ 40 mm Hg were associated with early mortality, while BAL lymphocytosis was associated with improved survival. A decline in FVC ≥ 5% (hazard ratio [HR]: 3.10, 95% CI: 2.00-4.81, p < 0.001), FVC ≥ 10% (HR: 3.11, 95% CI: 1.94-4.99, p < 0.001), DLCO ≥ 10% (HR: 2.80, 95% CI: 1.78-4.42, p < 0.001) and DLCO ≥ 15% (HR: 2.92, 95% CI: 1.18-4.72, p < 0.001) at 1 year was associated with markedly reduced survival on univariable and multivariable analyses after correcting for demographic variables, disease severity, honeycombing on CT and treatment, as well as BAL lymphocytosis and PASP ≥ 40 mm Hg on echocardiography, in separate models.ConclusionWorsening in FVC and DLCO at 1 year, including a marginal decline in FVC ≥ 5% and DLCO ≥ 10%, is predictive of markedly reduced survival in fHP.
Project description:Hypersensitivity pneumonitis (HP) is one of the most common interstitial lung diseases (ILD), that presents unique challenges for a confident diagnosis and limited therapeutic options. The disease is triggered by exposure to a wide variety of inciting antigens in susceptible individuals which results in T-cell hyperactivation and bronchioloalveolar inflammation. However, the genetic risk and the pathogenic mechanisms remain incompletely elucidated. Revised diagnostic criteria have recently been proposed, recommending to classify the disease in fibrotic and non-fibrotic HP which has strong therapeutic and outcome consequences. Confident diagnosis depends on the presence of clinical features of ILD, identification of the antigen(s), typical images on high-resolution computed tomography (HRCT), characteristic histopathological features, and lymphocytosis in the bronchoalveolar lavage. However, identifying the source of antigen is usually challenging, and HRCT and histopathology are often heterogeneous and not typical, supporting the notion that diagnosis should include a multidisciplinary assessment. Antigen removal and treating the inflammatory process is crucial in the progression of the disease since chronic persistent inflammation seems to be one of the mechanisms leading to lung fibrotic remodeling. Fibrotic HP has a few therapeutic options but evidence of efficacy is still scanty. Deciphering the molecular pathobiology of HP will contribute to open new therapeutic avenues and will provide vital insights in the search for novel diagnostic and prognostic biomarkers.
Project description:Hypersensitivity Pneumonitis (HP) one of the most common interstitial lung diseases (ILDs) is characterized by exposure to an inhaled inciting antigen that leads to a host immunologic reaction determining interstitial inflammation and architectural distortion. The underlying pathogenetic mechanisms are unclear. The absence of international shared diagnostic guidelines and the lack of a "gold-standard" test for HP combined with the presence of several clinical and radiologic overlapping features makes it particularly challenging to differentiate HP from other ILDs, also in expert contests. Radiology is playing a more crucial role in this process; recently the headcheese sign was recognized as a more specific for chronic-HP than the extensive mosaic attenuation. Several classification proposals and diagnostic models have been advanced by different groups, with no prospective validation. Therapeutic options for HP have been limited to antigen avoidance and immunosuppressant drugs over the last decades. Several questions about this condition remain unanswered and there is a need for more studies.