Risk factors associated with mortality in hypersensitivity pneumonitis: a meta-analysis.

BACKGROUND: Hypersensitivity pneumonitis (HP) related deaths have increased substantially in recent years. It is important to identify the risk factors of HP significantly associated with mortality to ensure close patient monitoring and assess disease progression. RESEARCH DESIGN AND METHODS: Extensive literature search was conducted in accordance with the PRISMA checklist. Literature search of PubMed, Embase, and Cochrane Library database between January 2009 and April 2021 using the terms 'hypersensitivity pneumonitis', 'hazard ratio', and 'mortality' identified 325 articles. A total of 22 independent original studies focusing on mortality of HP patients were assessed. RESULTS: This systematic review and meta-analysis suggests that increased age, male sex, honeycombing, and traction bronchiectasis patterns on high-resolution computed tomography (HRCT) images are the major mortality-related risk factors of patients with HP. In case of chronic HP, antigen exposure appeared to be an additional risk factor. CONCLUSIONS: The clinico-radiological risk factors of mortality identified for HP will enable effective and close monitoring of patients, prognostication, and guide toward appropriate management decisions. However, association between the type of antigen and mortality remains to be explored.

Acute exacerbation of fibrotic hypersensitivity pneumonitis: incidence and outcomes.

BACKGROUND: Patients with fibrotic hypersensitivity pneumonitis (HP) show variable clinical courses, and some experience rapid deterioration (RD), including acute exacerbation (AE). However, little is known about AE in fibrotic HP. Here, we retrospectively examined the incidence, risk factors, and outcomes of AE in fibrotic HP. METHODS: The incidence rates of AE were calculated in 101 patients with biopsy-proven HP. AE was defined as the worsening of dyspnoea within 30 days, with new bilateral lung infiltration and no evidence of infection or other causes of dyspnoea. RESULTS: During follow-up (median: 30 months), 18 (17.8%) patients experienced AE. The 1, 3, and 5 year incidence rates of AE were 6.0, 13.6, and 22.8%, respectively. Lower diffusing capacity of the lung for carbon monoxide (DLCO) and a radiologic usual interstitial pneumonia (UIP)-like pattern were risk factors for AE. In-hospital mortality after AE was 44.4%. Median survival from diagnosis was significantly shorter in patients with AE (26.0 months) than in those with no-AE RD (55.0 months; p = 0.008) or no RD (not reached; p < 0.001). AE remained a significant predictor of all-cause mortality (hazard ratio, 8.641; 95% confidence interval, 3.388-22.040; p < 0.001) after adjustment for age, body mass index, lung function, lymphocyte levels in bronchoalveolar lavage fluid, and the presence of a UIP-like pattern. CONCLUSIONS: AE was not uncommon among patients with fibrotic HP and significantly affected prognosis. A lower DLCO value and radiologic UIP-like pattern at diagnosis were associated with the development AE in patients with fibrotic HP.

Hypersensitivity Pneumonitis and (Idiopathic) Pulmonary Fibrosis Due to Feather Duvets and Pillows / Neumonitis por hipersensibilidad y fibrosis pulmonar (idiopática) debidas a los edredones y las almohadas de plumas

INTRODUCTION: Exposure to feather bedding may be an unnoticed cause of hypersensitivity pneumonitis (HP) and idiopathic pulmonary fibrosis (IPF). Thus, an in-depth clinical study of the diagnosis of patients with suspected HP and IPF is required in order to determine their etiologies. The objective of the present study is to raise awareness of HP and pulmonary fibrosis due to exposure to feather bedding, and to study the prevalence and describe long-term outcomes. METHODS: We describe a series of 33 patients diagnosed with HP and pulmonary fibrosis due to feather bedding exposure and followed over a 10-year period. The patients were from a subgroup of 127 individuals with HP undergoing in-depth evaluation using a diagnostic protocol at a regional referral center. RESULTS: Eleven (33%) patients were clinically diagnosed with acute HP and 22 (67%) with chronic HP. Ten (45%) chronic HP patients showed a high resolution computed tomography (HRCT) pattern of usual interstitial pneumonia (UIP) with suspected IPF. The prevalence of HP was 6.2/100 000 feather bedding users (compared with 54.6 per 100 000 bird-breeders). The survival rates of patients over the 10-year period was 100% for acute HP and 64% for chronic HP. CONCLUSIONS: In a series of HP patients, the diagnosis was attributed to feather bedding exposure in 26%. UIP pattern on HRCT was present in nearly half of the chronic cases. The survival of patients with chronic HP at ten years was 64%, despite avoiding further exposure

INTRODUCCIÓN: La exposición a la ropa de cama rellena de plumas puede ser una causa que pase inadvertida de neumonitis por hipersensibilidad (NH) y fibrosis pulmonar idiopática (FPI). Por lo tanto, se requiere un estudio clínico en profundidad durante el proceso diagnóstico de pacientes con sospecha de NH e FPI para determinar sus etiologías. El objetivo del presente estudio es crear conciencia sobre la NH y la fibrosis pulmonar debidas a la exposición a la ropa de cama rellena de plumas, y estudiar la prevalencia y describir los resultados a largo plazo. MÉTODOS: Describimos una serie de 33 pacientes diagnosticados con NH y fibrosis pulmonar debido a la exposición a la ropa de cama rellena de plumas y en seguimiento durante un período de 10 años. Los pacientes pertenecían a un subgrupo de 127 individuos con NH a los cuales se les estaba realizando una evaluación en profundidad utilizando un protocolo de diagnóstico en un centro de referencia regional. RESULTADOS: A 11 pacientes (33%) se les diagnosticó de NH aguda y a 22 (67%) de NH crónica. Diez de los pacientes con NH crónica (45%) mostraron un patrón de neumonía intersticial usual (NIU) en la tomografía computarizada de alta resolución (TCAR), con sospecha de FPI. La prevalencia de NH fue de 6,2/100.000 usuarios de ropa de cama rellena de plumas (en comparación con el 54,6 por cada 100.000 criadores de aves). Las tasas de supervivencia de los pacientes durante el período de 10 años fueron del 100% para la NH aguda y del 64% para la NH crónica. CONCLUSIONES: En una serie de pacientes con NH, el diagnóstico se atribuyó a la exposición a la ropa de cama rellena de plumas en un 26%. El patrón NIU en el TCAR estaba presente en casi la mitad de los casos crónicos. La supervivencia de los pacientes con NH crónica a los 10 años fue del 64%, a pesar de evitar posteriores exposiciones

Prognostic factors in chronic hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease resulting from exposure to inhaled environmental antigens. Prognosis is variable, with a subset of patients developing progressive fibrosis leading to respiratory failure and death. Therefore, there is an urgent need to identify factors which predict prognosis and survival in patients with HP. We undertook a narrative review of existing evidence to identify prognostic factors in patients with chronic HP. Patient demographics, smoking history, extent of antigen exposure and comorbidities all have reported associations with disease outcome, and physiological, radiological and laboratory markers have been shown to predict overall survival. While no single marker has been demonstrated to accurately and reliably predict prognosis, older age, more severe impairment of pulmonary function at baseline and established fibrosis on either biopsy or high-resolution computed tomography are consistently associated with worse survival. The vast majority of existing studies are retrospective, and this review identifies a need for prospective longitudinal studies with serial assessment of respiratory health to ascertain factors associated with nonfatal deterioration. Future developments, including the development of HP-specific composite scores may help further improve our ability to predict outcomes for individual patients.

Comorbidities and survival in patients with chronic hypersensitivity pneumonitis.

INTRODUCTION: Chronic Hypersensitivity Pneumonitis (cHP) is a fibrotic interstitial lung disease (ILD) resulting from repeated exposure to an offending antigen. Prognostication in cHP remains challenging, and the relationship between comorbidities and survival has yet to be characterized. The aim of this study was to describe the relationship between comorbid conditions and survival in patients with cHP. METHODS: The prospective database from a tertiary referral centre for ILD was reviewed for patient-reported comorbidities, their frequency, and relationship with survival in cHP patients. Comorbidities were assessed by direct questioning of the patient at the baseline visit and by a standardized questionnaire for the diagnosis of interstitial lung diseases. During the follow-up examinations, patients were asked about newly diagnosed comorbidities. RESULTS: Two hundred eleven patients with cHP were identified (mean age 63 years, 53% male, mean FVC 73%), with mean follow-up of 32 months. The mean number of comorbidities was 3 (10% had 0, 59% 1-3 and 31% ≥4 comorbidities). Most frequent comorbidities groups were cardiovascular (65%) and respiratory (26%), most common comorbidities were hypertension (56%), gastro-esophageal reflux disease (GERD) (24%), diabetes (20%) and coronary heart disease (18%). In general, deceased patients had more comorbidities than survivors (p = 0.005), yet there was no association between the absolute number of comorbidities and survival. Pulmonary hypertension (30.8% versus 5.7%, p = 0.001;), diastolic dysfunction (26.9% versus 6.4%, p = 0.004) and cerebrovascular disease were more frequent in non-survivors (23.1% versus 7.6%, p = 0.026). Lung cancer was not observed, and neither GERD nor antacid drugs were associated with outcome (p = 0.357 and p = 0.961, respectively). CONCLUSIONS: Comorbidities are common in cHP are associated with survival. Further work should determine whether interventions for these specific comorbidities can positively affect survival.

Change in Serum Biomarker CA 15-3 as an Early Predictor of Response to Treatment and Survival in Hypersensitivity Pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is an interstitial lung disease with a heterogeneous course of disease and treatment response. Cancer antigen 15-3 (CA 15-3), part of mucin 1, is believed to reflect epithelial cell injury and lung permeability and could be a potential biomarker for treatment response in HP. OBJECTIVE: To assess the value of CA 15-3 as a predictive biomarker in non-fibrotic and fibrotic HP during immunosuppressive therapy. DESIGN: Serum levels of CA 15-3 and pulmonary function tests (PFTs) were retrospectively retrieved from 48 HP patients treated with prednisone or cyclophosphamide at initiation of therapy (baseline), after 3 and 6 months. Pearson's correlation coefficient was computed to assess correlations between change in serum levels and PFT. Survival was evaluated using Kaplan-Meier curves. RESULTS: After 6 months of immunosuppressive therapy CA 15-3 levels decreased significantly compared to baseline (p = 0.001). Change in CA 15-3 after 6 months correlated with FVC change (r = - 0.469; p = 0.001). Correlations with FVC change were observed in prednisone-treated HP (r = - 0.514; p = 0.005) and fibrotic HP (r = - 0.417; p = 0.007). Three-month CA 15-3 change correlated with 6-month FVC change (r = - 0.599; p < 0.001). CA 15-3 declines of at least 7.9% after 6 months were associated with increased survival compared to minor CA 15-3 changes (HR 0.34; p = 0.020). CONCLUSION: Serum CA 15-3 correlates with PFT during 6 months of immunosuppressive therapy in HP. Interestingly, early CA 15-3 changes could predict future PFT. Furthermore, a decrease in CA 15-3 is related to longer survival. Therefore, serum CA 15-3 is a promising biomarker for implementation in HP care.

Comparative survival analysis between idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis.

INTRODUCTION: Chronic hypersensitivity pneumonitis (CHP) is an interstitial lung disease with limited treatment response and bad prognosis. Sometimes it is indistinguishable from idiopathic pulmonary fibrosis (IPF) becoming one of the main differential diagnosis. The aim of our study is to compare survival and functional decline between these two entities. METHODS: Survival and functional decline more than 10% in FVC were compared using Kaplan Meier (KM) method between patients with CHP and IPF. Cox proportional hazard analysis was used to identify independent predictors of survival and functional decline. RESULTS: 146 patients were included, 54 with CHP and 92 with IPF. KM rate for 2 years survival was 0.71 (CI 95% 0,6-0,8) for CHP group and 0,83 (CI 95% 0,66 - 0,92) for IPF (p=0,027). Nevertheless this difference disappeared using Cox proportional hazard analysis, the adjusted HR for survival among CHP patients was 0,53 (CI 95% 0,25-1,15) (p=0,11). There was no difference in functional evolution between the two groups. KM rate for a decline more than or equal to 10% was 0,64 for CHP (CI 95% 0,43-0,79) and 0,78 for IPF (IC 95% 0,6-0,88) (p=0,22). This observation did not change after using Cox proportional hazard analysis. CONCLUSIONS: Our study shows that both IPF and CHP are fibrosing interstitial diseases with a similar evolution and survival. It might be possible that therapeutic approach in patients with CHP should change in the light of these observations.

Clinical characteristics and outcomes of hypersensitivity pneumonitis: a population-based study in China.

BACKGROUNDS: Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD) that develops in response to the inhalation of various antigens. The clinical pathologies are very complex and undetermined. The clinical features and outcomes of HP have not been fully elucidated. The aim of this study was to analyze the incidence, clinical features, and outcomes of HP patients and construct a simple clinical model for diagnosing chronic HP (CHP). METHODS: The cohort study included 101 patients with HP admitted to the Nanjing Drum Tower Hospital from January 2009 to December 2017. The patients were categorized into acute HP (AHP, n = 72) and CHP (n = 29) groups according to the updated international criteria. The clinical, imaging, treatment, and follow-up data were retrospectively reviewed. All patients were followed up until December 31, 2017. Statistical analysis was performed, and a clinical scoring system for CHP was constructed by SPSS 20.0 software. RESULTS: The incidence of HP was 2.4% in ILD inpatients in our center. Patients in the CHP group were older (t = -2.212, P = 0.029), had more smokers (χ = 8.428, P = 0.004), and longer duration of symptoms (t = -4.852, P < 0.001) than those in the AHP group. Weight loss, crackles, digital clubbing, and cyanosis were more common in the CHP group than those in the AHP group (χ = 5.862, P < 0.001; χ = 8.997, P = 0.003; χ = 11.939, P = 0.001; and χ = 4.025, P = 0.045, respectively). On chest high-resolution computed tomography (HRCT), reticular patterns, traction bronchiectasis, and accompanying honeycombing were more common in CHP cases than those in AHP cases (χ = 101.000, P < 0.001; χ = 32.048, P < 0.001; and χ = 36.568, P < 0.001, respectively). The clinical scoring system for CHP was established based on the clinical variables (age [A], duration of symptoms [D], smoking history [S], unidentified exposure [U], and chest HRCT [C]; ADSUC) (area under the curve 0.935, 95% confidence interval: 0.883-0.987, P < 0.001). Eleven patients (15.3%) in the AHP group developed CHP, and unidentified exposure was an independent risk factor for the progression of disease (P = 0.038). The survival of patients with CHP, smoking history, unidentified antigens and fibrosis on Chest HRCT were significantly worse (P = 0.011, P = 0.001, P = 0.005, and P = 0.011, respectively) by Kaplan-Meier analysis. Cox multivariate regression analysis revealed that unidentified exposure and total lung volume (TLC pred%) were independent prognostic predictors for HP patients (P = 0.017 and P = 0.017, respectively). CONCLUSIONS: The clinical features and outcomes of the CHP patients differ from those of the AHP patients. ADSUC is a simple and feasible clinical model for CHP. Unidentified exposure is an independent risk factor for the progression of AHP to CHP. Unidentified exposure and a low baseline TLC pred% are independent predictors for survival in HP patients.

Hypersensitivity Pneumonitis: Radiologic Phenotypes Are Associated With Distinct Survival Time and Pulmonary Function Trajectory.

BACKGROUND: Hypersensitivity pneumonitis (HP) is an interstitial lung disease with a better prognosis, on average, than idiopathic pulmonary fibrosis (IPF). We compare survival time and pulmonary function trajectory in patients with HP and IPF by radiologic phenotype. METHODS: HP (n = 117) was diagnosed if surgical/transbronchial lung biopsy, BAL, and exposure history results suggested this diagnosis. IPF (n = 152) was clinically and histopathologically diagnosed. All participants had a baseline high-resolution CT (HRCT) scan and FVC % predicted. Three thoracic radiologists documented radiologic features. Survival time is from HRCT scan to death or lung transplant. Cox proportional hazards models identify variables associated with survival time. Linear mixed models compare post-HRCT scan FVC % predicted trajectories. RESULTS: Subjects were grouped by clinical diagnosis and three mutually exclusive radiologic phenotypes: honeycomb present, non-honeycomb fibrosis (traction bronchiectasis and reticulation) present, and nonfibrotic. Nonfibrotic HP had the longest event-free median survival (> 14.73 years) and improving FVC % predicted (1.92%; 95% CI, 0.49-3.35; P = .009). HP with non-honeycomb fibrosis had longer survival than IPF (> 7.95 vs 5.20 years), and both groups experienced a significant decline in FVC % predicted. Subjects with HP and IPF with honeycombing had poor survival (2.76 and 2.81 years, respectively) and significant decline in FVC % predicted. CONCLUSIONS: Three prognostically distinct, radiologically defined phenotypes are identified among patients with HP. The importance of pursuing a specific diagnosis (eg, HP vs IPF) among patients with non-honeycomb fibrosis is highlighted. When radiologic honeycombing is present, invasive diagnostic testing directed at determining the diagnosis may be of limited value given a uniformly poor prognosis.

Long-term outcomes in chronic hypersensitivity pneumonitis.

INTRODUCTION: The objective of this study was to analyze mortality, possible predictors of long-term survival, and health-related quality of life of a large chronic hypersensitivity pneumonitis (CHP) patient sample. METHODS: Longitudinal study in patients diagnosed with CHP during 2004-2013, followed for at least 1 year. Patients remaining alive and consenting to participate had a follow-up visit during 2015, including a complete pulmonary function study and the EuroQol-5D and Beck Depression and Anxiety Inventories. RESULTS: Out of the 160 patients finally included, 87 remained alive. Seventy-three had died or underwent lung transplantation at the time of the study with a median survival of 7.0 (4.4-14.5) years. A Cox proportional risk model showed that factors associated with lower survival were as follows: increased age, a low percentage of lymphocytes in bronchoalveolar lavage (BAL), a decreased transfer factor of the lung for carbonmonoxide (DLCO), presence of honeycomb in the high-resolution chest scan (HRCT), and the usual interstitial pneumonia (UIP) histologic pattern. At follow-up, all patients presented an EuroQol-5D score <0.8 and 21(50%) and 9(28.6%) subjects presented a probable anxiety and depressive syndrome, respectively. CONCLUSION: CHP is a severe disease with a bad mid-term prognosis. Lymphocyte values in BAL and DLCO values at baseline, presence of honeycomb in HRCT, and UIP histologic pattern were found to be predictors of survival. Early accurate diagnosis of the disease is fundamental for prompt initiation of antigen avoidance.

Clinical behaviour of patients exposed to organic dust and diagnosed with idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Although idiopathic pulmonary fibrosis (IPF) patients experience a worse survival compared with chronic hypersensitivity pneumonitis (CHP), organic dust exposure is a known risk factor for both IPF and CHP. METHODS: We divided patients diagnosed with IPF, based on their exposure to moulds/birds (absent: group A; present: group B). We retrospectively compared pulmonary function and survival between groups A and B, and a separate CHP cohort (group C). RESULTS: A total of 293 patients were included (group A: n = 171, group B: n = 73, group C: n = 49). Demographics and baseline pulmonary function did not differ between groups A and B, but significant differences were seen between groups B and C. Median survival of group B was 84 months, which was longer than group A (43 months, P = 0.002), but lower than group C (157 months, P = 0.04), in both univariate and multivariate analyses. Antifibrotic treatment resulted in a better outcome in group A (hazard ratio (HR): 0.44) and group B (HR: 0.12) without interaction between exposure and antifibrotic use (P = 0.20). Forced vital capacity (FVC) decline was not associated with mould/bird exposure in this cohort. CONCLUSION: Group B patients experienced a better outcome compared with (non-exposed) IPF patients, although worse compared with CHP patients. Antifibrotic treatment in group B resulted in a similar beneficial effect compared with group A. Further research is needed to ascertain the diagnostic designation in this exposed usual interstitial pneumonia (UIP) patient group without other CHP features.

Epidemiology of Hypersensitivity Pneumonitis among an Insured Population in the United States: A Claims-based Cohort Analysis.

RATIONALE: Hypersensitivity pneumonitis is a complex lung disease resulting from repeated inhalation of a variety of antigens. Limited data exist regarding its epidemiology. OBJECTIVES: To describe the trends in the annual incidence and prevalence of hypersensitivity pneumonitis in the United States. METHODS: We developed novel claims-based coding algorithms to identify hypersensitivity pneumonitis, chronic hypersensitivity pneumonitis, and fibrotic hypersensitivity pneumonitis cases using the 2004 to 2013 MarketScan Commercial and Medicare Supplemental healthcare claims databases. Algorithm validity and reliability were assessed with clinical data from National Jewish Health. We calculated yearly cumulative incidence and prevalence overall and by age. For the subgroup with vital status, Kaplan-Meier methods were used to analyze survival stratified by evidence of fibrosis. RESULTS: We identified 7,498 cases that met our hypersensitivity pneumonitis definition over the 10-year study period, including 3,902 with chronic hypersensitivity pneumonitis and 1,852 with fibrotic hypersensitivity pneumonitis. On the basis of the clinical-radiological adjudication of the validation sample, 38 cases (95%) were confirmed as hypersensitivity pneumonitis. The mean age was 52 years, and 58% were women. The 1-year prevalence rates for hypersensitivity pneumonitis ranged from 1.67 to 2.71 per 100,000 persons, and 1-year cumulative incidence rates ranged from 1.28 to 1.94 per 100,000 persons. The prevalence increased with age, ranging from 0.95 per 100,000 among 0- to 9-year-olds to 11.2 per 100,000 among those aged 65 years and older. Between 56 and 68% of hypersensitivity pneumonitis cases in each year were classified as chronic hypersensitivity pneumonitis (prevalence, 0.91-1.70 per 100,000 persons; cumulative incidence, 0.63-1.08 per 100,000 persons). Fewer had fibrotic hypersensitivity pneumonitis (prevalence, 0.41-0.80 per 100,000 persons; cumulative incidence: 0.29-0.43 per 100,000 persons). Most cases (74%) were classified as unspecified hypersensitivity pneumonitis. Older age, male sex, and fibrosis were associated with higher mortality rates in unadjusted analyses. CONCLUSIONS: Using U.S. administrative claims-based data, we developed an algorithm with a high sensitivity and specificity for hypersensitivity pneumonitis. Between 2004 and 2013, hypersensitivity pneumonitis was more common among women and those older than 65 years. Most cases were classified as chronic hypersensitivity pneumonitis. Approximately one-fourth met our criteria for fibrotic hypersensitivity pneumonitis, which was associated with a higher mortality rate.

The MUC5B promoter polymorphism and telomere length in patients with chronic hypersensitivity pneumonitis: an observational cohort-control study.

BACKGROUND: Patients with hypersensitivity pneumonitis are at risk of developing pulmonary fibrosis, which is associated with reduced survival. In families with multiple affected members, individuals might be diagnosed as having idiopathic pulmonary fibrosis (IPF) or chronic (fibrotic) hypersensitivity pneumonitis, which suggests these disorders share risk factors. We aimed to test whether the genomic risk factors associated with the development and progression of IPF are also associated with the development of fibrosis and reduced survival in people with chronic hypersensitivity pneumonitis. METHODS: We did an observational study of two independent cohorts of patients with chronic hypersensitivity pneumonitis, one from the University of California San Francisco, CA, USA (UCSF), and one from the University of Texas Southwestern, TX, USA (UTSW). We measured two common single-nucleotide polymorphisms associated with IPF (MUC5B rs35705950 and TOLLIP rs5743890) and telomere length in peripheral blood leucocytes, and assessed their associations with chronic hypersensitivity pneumonitis risk, survival, and clinical, radiographic, and pathological features. We compared findings with those in patients with IPF from the UCSF and UTSW cohorts, and healthy controls from the European population of the 1000 Genomes Project Phase 3, version 1. FINDINGS: The cohorts included 145 patients from UCSF and 72 from UTSW. The minor allele frequency (MAF) was greater for MUC5B rs35705950 in patients with chronic hypersensitivity pneumonitis than in healthy controls (24·4% in UCSF and 32·3% in UTSW vs 10·7%, both p<0·0001), but not for TOLLIP rs5743890. The MAFs were similar to those for IPF (UCSF 33·3%, p=0·09; UTSW 32·0%, p=0·95). In the combined UCSF and UTSW chronic hypersensitivity pneumonitis cohort, we saw associations between extent of radiographic fibrosis and MUC5B rs35705950 minor alleles (adjusted odds ratio [OR] 1·91, 95% CI 1·02-3·59, p=0·045) and short telomere length (adjusted OR per unit change in mean natural logarithm-transformed ratio of telomere repeat copy number to single gene copy number 0·23, 0·09-0·59, p=0·002). Telomere length less than the tenth percentile for age was also significantly associated with reduced survival (log-rank p=0·006). INTERPRETATION: The associations between MUC5B rs35705950 and short telomere length with extent of fibrosis, histopathological features of usual interstitial pneumonia, and reduced survival in patients with chronic hypersensitivity pneumonitis suggest shared pathobiology with IPF, and might help to stratify risk. FUNDING: National Institutes of Health and Nina Ireland Program for Lung Health.

Presence of Air Trapping and Mosaic Attenuation on Chest Computed Tomography Predicts Survival in Chronic Hypersensitivity Pneumonitis.

RATIONALE: Significant heterogeneity of computed tomography (CT) presentation exists within chronic hypersensitivity pneumonitis (HP). There are limited data aimed at delineating the prognostic value of specific CT features, distribution, and patterns in chronic HP. OBJECTIVES: To examine whether the presence of CT mosaic attenuation (MA) and air trapping (AT), and the distribution or patterns of fibrosis impact survival in subjects with chronic HP. METHODS: We retrospectively identified 110 consecutively enrolled, well-characterized, biopsy-proven adult subjects with chronic HP between 1982 and 2015 from the National Jewish Health interstitial lung disease research database. The first available CT scan of diagnostic quality from each subject was formally evaluated for specific CT findings associated with chronic HP and for overall CT pattern. A Cox proportional hazards model was used to identify independent predictors in time-to-death analysis, and bootstrap analysis was performed for internal model validation. RESULTS: Fibrotic HP (65%; 72/110) was most often peripheral in the axial plane and lower lung preponderant. The distribution of lung disease in those without fibrosis was most often axially and zonally diffuse. There was no association between survival and CT distribution or CT pattern in the whole cohort or within the fibrotic subset of subjects. After multivariate adjustment, AT/MA was independently associated with survival in the whole cohort (HR = 0.26; 95% confidence interval = 0.07-0.97). Results were similar after restricting the analyses to fibrotic HP cases. CONCLUSIONS: Among subjects with chronic HP, the presence of CT AT/MA may identify subjects with better prognosis.

Chronic hypersensitivity pneumonitis: identification of key prognostic determinants using automated CT analysis.

BACKGROUND: Chronic hypersensitivity pneumonitis (CHP) has a variable disease course. Computer analysis of CT features was used to identify a subset of CHP patients with an outcome similar to patients with idiopathic pulmonary fibrosis (IPF). METHODS: Consecutive patients with a multi-disciplinary team diagnosis of CHP (n = 116) had pulmonary function tests (FEV1, FVC, DLco, Kco, and a composite physiologic index [CPI]) and CT variables predictive of mortality evaluated by analysing visual and computer-based (CALIPER) parenchymal features: total interstitial lung disease (ILD) extent, honeycombing, reticular pattern, ground glass opacities, pulmonary vessel volume (PVV), emphysema, and traction bronchiectasis. Mean survival was compared between both CHP and IPF patients (n = 185). RESULTS: In CHP, visual/CALIPER measures of reticular pattern, honeycombing, visual traction bronchiectasis, and CALIPER ILD extent were predictive of mortality (p < 0 · 05) on univariate analysis. PVV was strongly predictive of mortality on univariate (p < 0 · 0001) and multivariate analysis independent of age, gender and disease severity (represented by the CPI [p < 0 · 01]). CHP patients with a PVV threshold >6 · 5% of the lung had a mean survival (35 · 3 ± 6 · 1 months; n = 20/116 [17%]) and rate of disease progression that closely matched IPF patients (38 · 4 ± 2 · 2 months; n = 185). CONCLUSIONS: Pulmonary vessel volume can identify CHP patients at risk of aggressive disease and a poor IPF-like prognosis.

Pathologic Findings and Prognosis in a Large Prospective Cohort of Chronic Hypersensitivity Pneumonitis.

BACKGROUND: The ability of specific histopathologic features to predict mortality or lung transplantation in patients with chronic hypersensitivity pneumonitis (HP) is unknown. METHODS: Patients with chronic HP diagnosed by surgical lung biopsy were identified from an ongoing longitudinal cohort. The surgical lung biopsy slides were evaluated prospectively by an experienced thoracic pathologist using a standardized checklist to differentiate the major pathologic patterns and score the presence of specific histopathologic features. Cox proportional hazard analysis was used to identify independent predictors of transplant-free survival, and Kaplan-Meier analysis was used to visualize outcomes. RESULTS: One hundred nineteen patients were identified. Patients with a fibrotic nonspecific interstitial pneumonia (f-NSIP) pattern, bronchiolocentric fibrosis (BF) pattern, or usual interstitial pneumonia (UIP) pattern had significantly worse transplant-free survival than did those with a cellular NSIP (c-NSIP) pattern or peribronchiolar inflammation with poorly formed granulomas (PI-PFG) pattern. No survival difference among patients with an f-NSIP pattern, a BF pattern, or a UIP pattern was found. Fibroblastic foci were identified in a subset of biopsy samples from all pathologic patterns. Peribronchiolar fibrosis was noted in all UIP cases. Independent predictors of time to death or transplantation included the presence of fibroblast foci or dense collagen fibrosis. CONCLUSIONS: Histopathologic patterns of c-NSIP and PI-PFG had a better transplant-free survival than did patterns of UIP, f-NSIP, and BF. The presence of fibroblast foci or dense collagen fibrosis correlated with progression to death or lung transplantation. Identification of fibroblast foci on biopsy samples, regardless of the underlying histopathologic pattern, may be a clinically useful predictor of survival in patients with HP.