Incidence and changes in treatment of acute exacerbation of idiopathic pulmonary fibrosis in Japan: A claims-based retrospective study

BackgroundAcute exacerbation is an essential prognostic factor in idiopathic pulmonary fibrosis (IPF) and is the leading cause of death in Japanese patients with IPF. Its epidemiology, treatment status, and effect on IPF progression have been insufficiently investigated. We examined the incidence of acute exacerbation and treatment status before and after the onset of acute exacerbation in Japanese patients with IPF to provide basic information for treatment strategies.MethodsA Japanese claims database (April 2008–March 2019) from acute-care hospitals was analyzed. Incidence of acute exacerbation, time to the next event, and percentages of patients who received each treatment by the year before and after the onset of acute exacerbation were examined in patients diagnosed with IPF at least once. Acute exacerbation was defined according to the use of steroid pulse therapy.ResultsWe identified 9961 patients with IPF and 2629 acute exacerbations (average age at the time of acute exacerbation: 74.8 years, percentage of men: 79%). The annual incidence of acute exacerbation was approximately 10% between 2010 and 2018. The time to the next acute exacerbation shortened with increasing number of these events. The percentage of patients receiving antifibrotic drugs remained constant (30%–40%) throughout the period. The percentages of patients receiving steroid therapy, immunosuppressive drugs, and oxygen therapy increased after the onset of acute exacerbation compared with before the onset.ConclusionsThe annual incidence of acute exacerbation was approximately 10% in recent years. It is suggested that acute exacerbation worsens respiratory function in patients with IPF.     

Characteristics and association with survival of respiratory-related hospitalization in Japanese idiopathic pulmonary fibrosis patients

BackgroundThe characteristics and significance of respiratory-related hospitalization in patients with idiopathic pulmonary fibrosis (IPF) in Asian countries remain unknown. The purpose of this study was to define the characteristics of respiratory-related hospitalization and to inspect the relationship between respiratory-related hospitalization and subsequent survival in patients with IPF in Japanese general practice.MethodsPatients with IPF who underwent clinical evaluation between February 2008 and August 2017 were screened. Only those who had undergone evaluation within 1 year after the diagnosis of IPF were included in the study. The post-diagnosis pulmonary function tests were considered the registration point. We then performed a 6-month landmark analysis including only patients who were alive 6 months after the registration. The characteristics of respiratory-related hospitalizations during the 6 months after registration and the association between respiratory-related hospitalization and survival were investigated.ResultsA total of 106 patients with IPF were included in the study. The mean forced vital capacity (FVC) at registration was 80.2 ± 25.1% predicted. Seventeen patients (16.0%) had respiratory-related hospitalization during the 6 months after registration. Pneumonia was the most frequent reason for hospitalization (47.0%), followed by acute exacerbation of IPF (29.4%). In multivariate analysis, % predicted FVC (hazard ratio: 0.98, 95% confidence interval: 0.96–0.99, p = 0.004), 6-month decrease in % predicted FVC (1.05, 1.02–1.08, 0.005), and respiratory-related hospitalization (2.45, 1.24–4.85, 0.009) were significantly associated with survival.ConclusionsPneumonia is the most frequent cause of respiratory-related hospitalization in Japanese IPF patients. Furthermore, respiratory-related hospitalization is significantly associated with subsequent poor survival.     

Predictors of acute exacerbation in biopsy-proven idiopathic pulmonary fibrosis

BackgroundAcute exacerbation (AE) is a major cause of death in patients with idiopathic pulmonary fibrosis (IPF). Current evidence on AE-IPF has been largely based on clinical, rather than pathological, analyses.MethodsWe investigated AE incidence and its predictors using clinical, radiological, and pathological data of patients diagnosed with IPF by multi-disciplinary discussion.This study, a secondary analysis of previous research, included 155 patients with IPF who underwent surgical lung biopsy (SLB). Cumulative AE incidence was evaluated by the Kaplan–Meier method. Predictors of AE-IPF were analyzed with a Fine-Gray sub-distribution hazard model. Sub-analysis was performed using propensity score-matching analysis.ResultsIn this cohort, the median age of the patients was 66 years and the median percent-predicted forced vital capacity was 82.8%. The cumulative AE incidence rates at 30 days and one year post SLB were 1.9% and 7.6%, respectively. On multivariable analysis, a lower percent-predicted diffusing capacity of the lung for carbon monoxide (%DL_CO) (hazard ratio 0.98 per 1% increase, P = 0.02) and fibroblastic foci (FF)-present (vs. absent; hazard ratio 3.01, P = 0.04) were independently associated with a higher incidence of AE. The propensity score-matching analysis with adjustment for age, gender, and %DL_CO revealed that the cumulative AE incidence rate was significantly higher in the FF-present subgroup than in the FF-absent subgroup (1-year incidence rate, 10.5% vs. 0%, respectively; P = 0.04 by Gray's test).ConclusionsFF and %DL_CO were independent predictors of AE in patients with biopsy-proven IPF. FF may be associated with the pathogenesis of AE-IPF.     

Safety and tolerability of combination therapy with pirfenidone and nintedanib for idiopathic pulmonary fibrosis: A multicenter retrospective observational study in Japan

BackgroundPhase IV clinical trials in Western countries have reported that combined therapy with pirfenidone and nintedanib for idiopathic pulmonary fibrosis (IPF) has a manageable safety profile. However, data on the long-term safety and tolerability of this combination treatment in the real-world setting in Japan are limited.MethodsThe retrospective data of 46 patients with IPF who received combination therapy with pirfenidone and nintedanib were obtained from 16 institutes in Japan. Adverse events and adverse drug reactions (ADRs) were reported through a retrospective review of medical records.ResultsNintedanib and pirfenidone were added to preceding treatment with antifibrotic drugs in 32 (69.6%) and 13 (28.3%) patients, respectively. In one patient (2.1%), the two drugs were concurrently initiated. The mean duration of monotherapy before initiating the combination was 26.3 months. In 26 of 38 patients (68.4%), the Gender–Age–Physiology index stage was II or III. Thirty-three patients (71.7%) had some ADRs, and 14 patients (30.4%) permanently discontinued either drug or both drugs owing to the development of ADRs during the observation period (mean: 59 weeks). The percentage of grade III or IV IPF according to the Japanese Respiratory Society severity classification was higher in patients who permanently discontinued either drug or both drugs than in those who continued both drugs (90.9% [10/11; 3 undetermined grade] vs. 61.1% [11/18; 1 undetermined grade]). Decreased appetite (18/46, 39.1%) and diarrhea (16/46, 34.8%) were frequently observed ADRs. Two patients (4.3%) had serious ADRs (liver toxicity and pneumothorax).ConclusionsReal-world data imply that combination therapy with pirfenidone and nintedanib for IPF has a manageable safety/tolerability profile.     

Serial 6-month change in forced vital capacity predicts subsequent decline and mortality in Japanese patients with newly diagnosed idiopathic pulmonary fibrosis

BackgroundThe clinical course of idiopathic pulmonary fibrosis (IPF) is characterized by a progressive decline in lung function; however, predicting changes in lung function is difficult. We sought to determine whether the prior 6-month trend in forced vital capacity (FVC) could predict mortality and the subsequent 6-month trend in FVC.MethodsWe retrospectively analyzed consecutive patients with newly diagnosed IPF who underwent serial pulmonary function tests. The immediate two years after the initial evaluation were divided into four terms of six months each and stratified on the basis of presence or absence of a ≥10% relative decline in FVC at six months (declined and stable groups, respectively).ResultsWe included 107 patients with %predicted FVC of 80.8% and %predicted diffusing capacity of the lung for carbon monoxide of 58.9%. In multivariate analysis, a decline in %predicted FVC in the initial six months was found to be an independent prognostic factor (hazard ratio 4.45, 95% confidence interval 2.62–7.56, p < 0.01). Among the 46 terms in which the FVC declined during the initial 1.5-year study period, a decline in FVC was exhibited in 23 (50.0%) of the subsequent terms. Among 231 terms in which FVC remained stable, a decline was observed in 32 (13.9%) of the subsequent terms (relative risk 3.61, p < 0.01). The frequency of FVC decline in each term was 16–27%. FVC was stable or declined in all four terms in 50.5% and 15.9% of cases, respectively.ConclusionsSix-month decline in FVC predicts subsequent FVC change and mortality in IPF patients in the era of antifibrotic agents.     

A modified GAP model for East-Asian populations with idiopathic pulmonary fibrosis

BackgroundThe easy-to-calculate gender, age, and lung physiology (GAP) model shows good predictive and discriminative performance in the prognosis of idiopathic pulmonary fibrosis (IPF). However, the GAP model was not effective in predicting the prognosis accurately in previous Japanese and Korean IPF cohort studies. Therefore, we developed a modified GAP model for the East-Asian populations by weighing the GAP variables. The validity of the modified GAP model was subsequently evaluated in East-Asian IPF patients.MethodsThe derivation cohort comprised 326 patients with IPF. Weights of the variables were adjusted on the basis of coefficients derived from Cox regression models. The total points were distributed to the three stages of the disease so that the number of patients included in each stage was appropriate. The validity of the modified model was analyzed in another Japanese cohort of 117 patients with IPF and a nationwide cohort of Korean patients with IPF.ResultsPredicted survival rates differed significantly in the derivation cohort using the modified GAP model for each stage of IPF (log-rank test: stage I vs. stage II, p < 0.001; stage II vs. stage III, p < 0.001). Model performance improved according to Harrell's C-index (at three years: 0.696 in the original GAP model to 0.738 in the modified model). The performance of the modified model was validated in the Japanese validation and Korean national cohorts.ConclusionsOur modification of the original GAP model showed improved performance in East-Asian IPF patient populations.     

Clinical course and prognosis in survivors of acute exacerbations of idiopathic pulmonary fibrosis

BackgroundPatients with idiopathic pulmonary fibrosis (IPF) are at risk of acute exacerbations (AEs) that manifest as respiratory distress. However, the clinical course after AEs of IPF (AE-IPFs) has not been well described. Therefore, we aimed to elucidate the clinical course and prognosis in survivors of AE-IPFs.MethodsConsecutive patients with IPF who presented to our institution with their first AE-IPFs between January 2008 and December 2019 were included in this study. Data were retrospectively collected, and the clinical course, survival, and cause of death were further analyzed.ResultsNinety-seven patients were included in this retrospective study. Among them, 67 (69.1%) were discharged alive, with a median survival time after discharge of 1081 days. AE recurrence and pneumonia were the most common causes of death, each accounting for 22.2% of cases among survivors of AE-IPFs. AEs were the most frequent during the first 3 years after discharge, whereas pneumonia was more common thereafter.ConclusionsSurvivors of AE-IPFs have a relatively favorable long-term prognosis. Among the survivors of first AE-IPFs, AE recurrence and pneumonia were the most common causes of death after discharge. Therefore, preventing AE recurrence and lung infections is crucial for prolonging survival in survivors of AE-IPFs.     

Pulse oximetry saturation can predict prognosis of idiopathic pulmonary fibrosis

BackgroundIn Japan, the severity staging system for idiopathic pulmonary fibrosis (IPF) has been used to determine medical care subsidies. However, this system requires invasive procedures to measure arterial oxygen tension. Recently, noninvasive and simple measurements of oxygen saturation by pulse oximetry (SpO₂) have been used for severity assessments. We propose a pulse oximetry saturation (POS) staging system consisting of SpO₂ parameters to predict prognosis.MethodsWe developed four prototype staging systems based on SpO₂ at rest and desaturation, and adopted the system with the highest C-statistic as the POS staging system. The cutoff SpO₂ values at rest were 96% and 90%, and desaturation was defined as SpO₂ < 90% at the end of the 6-min-walk test.ResultsTwo-hundred and nineteen IPF patients were studied and the C-statistic values of models 1, 2, 3, and 4 were 0.633, 0.643, 0.630, and 0.673, respectively. We judged model 4 to be a superior POS staging system; it defined SpO₂ ≥ 96% at rest without desaturation as stage Ⅰ; SpO₂ ≥ 96% at rest with desaturation or SpO₂ 90%–95% at rest without desaturation as stage Ⅱ; and SpO₂ 90%–95% at rest with desaturation or SpO₂ < 90% at rest as stage Ⅲ. The hazard ratios of POS stage Ⅰ, Ⅱ, and Ⅲ were 1.00, 2.25, and 4.99, respectively. The C-statistic of the POS staging system produced from 1000 bootstrap samples was similar (0.673), suggesting good internal validation.ConclusionA noninvasive and simple POS staging system defined by SpO₂ can easily predict prognosis.     

Hierarchical cluster analysis based on disease-associated manifestations of patients with lymphangioleiomyomatosis: An analysis of the national database of designated intractable diseases of Japan

BackgroundLymphangioleiomyomatosis (LAM) is a rare multisystem disease with variable manifestations and differing rates of progression among individuals. Classification of its phenotypes is an issue for consideration. We hypothesized that clinical manifestations associated with LAM cluster together and identifying these associations would be useful for identifying phenotypes.MethodsUsing cross-sectional data from the National Database of Designated Intractable Diseases of Japan, we performed a hierarchical cluster analysis based on disease-associated manifestations.ResultsFour clusters were identified from 404 patients (50.4% of 801 LAM patients registered in 2016). Patients in cluster 1 had only dyspnea on exertion, relatively low lung function, the earliest onset age, and the lowest prevalence of tuberous sclerosis complex (TSC). Those in cluster 2 had various manifestations with the highest prevalence of TSC. Patients in cluster 3 had major respiratory symptoms (cough, sputum, or dyspnea on exertion) or fatigue and the lowest lung function. Those in cluster 4 were asymptomatic and had the latest onset age, shortest disease duration, and relatively high prevalence of TSC. Patients in cluster 1 had the highest rate of receiving mechanistic target of rapamycin (mTOR) inhibitor treatment, suggesting that cluster 1 included those with declining lung function for which mTOR inhibitor treatment was required.ConclusionsHierarchical cluster analysis based on manifestations data identified four clusters. The characteristics of cluster 1 are noteworthy in relation to the indication for mTOR inhibitor treatment. A cluster analysis of accumulated and longitudinal data that allows valid clustering and outcome comparisons is required in the future.     

Extent of pulmonary fibrosis on high-resolution computed tomography is a prognostic factor in patients with pleuroparenchymal fibroelastosis

BackgroundSeveral prognostic factors for pleuroparenchymal fibroelastosis (PPFE) have recently been reported. However, detailed high-resolution computed tomography (HRCT) findings have not yet been evaluated as prognostic factors. This study retrospectively investigated whether HRCT findings are prognostic factors in patients with PPFE compared to those with idiopathic pulmonary fibrosis (IPF).MethodsPatients with PPFE and IPF diagnosed at our hospital between January 2008 and December 2016 were enrolled. Clinical and HRCT characteristics were obtained. In addition to our patients, we also analyzed data of PPFE patients whose cause of death had been identified in previous studies.ResultsWe enrolled 15 patients with PPFE and 75 patients with IPF. Consolidation and maximum pleural thickening were significantly higher in patients with PPFE than in those with IPF (both P < .001). Fibrosis score, honeycomb area, and traction bronchiectasis were not significantly different between these patient groups but were significant prognostic factors in patients with PPFE in univariate analysis (P = .021, P = .017, and P = .014, respectively). The proportions of deaths by acute exacerbation or lung cancer were significantly lower in patients with PPFE than in those with IPF (P < .001 and P = .001, respectively), whereas death by respiratory failure was significantly more frequent in PPFE patients (P < .001).ConclusionsHRCT findings, such as fibrosis score, honeycomb area, and traction bronchiectasis, were independent prognostic factors in patients with PPFE. Respiratory failure, but not acute exacerbation and lung cancer, was the main cause of death in patients with PPFE.     

The role of viral infections in pulmonary exacerbations of patients with non-cystic fibrosis bronchiectasis: A systematic review

BackgroundBronchiectasis is a cause of increased morbidity of the respiratory system. Exacerbations among patients with non-CF (cystic fibrosis) bronchiectasis result in reduced pulmonary function and poor quality of life. While the role of bacteria in triggering exacerbations in patients with non- CF bronchiectasis has been well studied, little is known about viral infections in these patients. We aimed to review the evidence on the role of respiratory viruses in the exacerbations of non-CF bronchiectasis.MethodsRelevant literature was searched on the MEDLINE/PubMed database. Seven studies satisfied the criteria and were included in this review.ResultsAccording to the included articles, respiratory viruses are often identified in exacerbations of patients with non-CF bronchiectasis with the most frequent being human rhinovirus and influenza viruses. When a virus is isolated during an exacerbation patients have more symptoms from the upper respiratory tract. One study showed that detection of Epstein- Barr virus among patients with non-CF bronchiectasis is correlated with faster reduction of pulmonary function and progression of the disease.ConclusionViruses seem to have a role in the exacerbation of patients with non-CF bronchiectasis. However, the exact nature and importance of this role remain elusive. Viruses are also isolated during the stable period of the disease. Further well-designed studies are necessary to clarify this complex issue.     

Serum S100A8 and S100A9 as prognostic biomarkers in acute exacerbation of idiopathic pulmonary fibrosis

BackgroundAcute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a devastating and life-threatening condition during its clinical course. Biomarkers for precisely anticipating the prognosis of AE-IPF remain to be fully established. The objective of this study was to clarify whether S100A8 and S100A9, which are calcium-binding proteins mainly produced by activated neutrophils, are significant prognostic biomarkers in AE-IPF.MethodsThirty-seven patients with AE-IPF who were diagnosed and treated at our hospital were retrospectively evaluated. The serum levels of S100A8 and S100A9 were measured using enzyme-linked immunosorbent assay, and the relationships between these levels and clinical parameters or prognosis were evaluated.ResultsThe serum levels of S100A8 (median 386.5 ng/mL) and S100A9 (median 60.2 ng/mL) in patients with AE-IPF were significantly higher than those in age-matched healthy controls and in patients at IPF diagnosis (p < 0.001 for all combinations). The serum levels of S100A8 negatively correlated with percent forced vital capacity (r = −0.356, p = 0.049) and positively correlated with peripheral white blood cell number (r = 0.509, p = 0.002). Immunohistochemical staining of autopsy lung specimens showed that neutrophils, present mainly in the alveolar septum, were positive for S100A8 and S100A9. Patients with AE-IPF with higher levels of S100A8 or S100A9 showed significantly worse 3-month survival than those with lower levels (log-rank test, both p = 0.028). Finally, in multivariate analysis, the serum levels of both S100A8 and S100A9 were significant prognostic factors (hazard ratio 4.032, p = 0.023 and hazard ratio 4.327, p = 0.012).ConclusionThe serum levels of S100A8 and S100A9 at AE were significant prognostic biomarkers in patients with AE-IPF.     

Idiopathic pulmonary fibrosis: Molecular mechanisms and potential treatment approaches

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease with high mortality that commonly occurs in middle-aged and older adults. IPF, characterized by a decline in lung function, often manifests as exertional dyspnea and cough. Symptoms result from a fibrotic process driven by alveolar epithelial cells that leads to increased migration, proliferation, and differentiation of lung fibroblasts. Ultimately, the differentiation of fibroblasts into myofibroblasts, which synthesize excessive amounts of extracellular matrix proteins, destroys the lung architecture. However, the factors that induce the fibrotic process are unclear. Diagnosis can be a difficult process; the gold standard for diagnosis is the multidisciplinary conference. Practical biomarkers are needed to improve diagnostic and prognostic accuracy. High-resolution computed tomography typically shows interstitial pneumonia with basal and peripheral honeycombing. Gas exchange and diffusion capacity are impaired. Treatments are limited, although the anti-fibrotic drugs pirfenidone and nintedanib can slow the progression of the disease. Lung transplantation is often contraindicated because of age and comorbidities, but it improves survival when successful. The incidence and prevalence of IPF has been increasing and there is an urgent need for improved therapies. This review covers the detailed cellular and molecular mechanisms underlying IPF progression as well as current treatments and cutting-edge research into new therapeutic targets.     

Real-world evaluation of asthma reliever therapy among continuous users of asthma maintenance medication in Japan: A retrospective cohort study using a claims database

BackgroundThe decrease in mortality rate owing to asthma has slowed in recent years. A large proportion of patients with asthma remain uncontrolled in Japan. This study aimed to determine the prevalence of short-acting beta 2 agonists (SABA) overuse and its associated factors.MethodsThis large-scale retrospective cohort study analyzed continuously treated patients with asthma aged 15–74 years between January 2017 and December 2017 using a Japanese insurance claims database. Characteristics, disease information, and prescribed drugs were extracted from the database, and treatment steps were defined according to drug combinations based on the criteria of the Japanese asthma guidelines. SABA overuse was defined as ≥3 canisters per year. Factors associated with SABA overuse were estimated using multivariable logistic regression.ResultsAmong 7,483 patients with mild-to-moderate asthma, 7,001 (93.6%) and 482 (6.4%) had low and high SABA use, respectively. Inhaled corticosteroids (ICS)/long-acting β-agonists (LABA) were the main asthma control treatments. The proportions of patients who overused SABA were 347 (9.9%) and 1,201 (5.6%) in the ICS and ICS/LABA groups, respectively. The factors associated with SABA overuse were male sex, ICS monotherapy, higher treatment steps, no history of allergic rhinitis, no history of chronic sinusitis, and no asthma management.ConclusionsThere is a relatively low prevalence of SABA overuse among asthmatic patients in Japan. ICS/LABA therapy, treatment steps, allergic rhinitis, chronic sinusitis, and asthma management are associated with a decreased risk of SABA overuse. Further studies are needed to investigate the association between SABA overuse and asthma exacerbation and mortality.     

Treatment strategies with alternative treatment options for patients with Mycobacterium avium complex pulmonary disease

Diseases caused by Mycobacterium avium complex (MAC) infection in the lungs are increasing worldwide. The recurrence rate of MAC-pulmonary disease (PD) has been reported to be as high as 25–45%. A significant percentage of recurrences occurs because of reinfection with a new genotype from the environment. A focus on reducing exposure to MAC organisms from the environment is therefore an essential component of the management of this disease as well as standard MAC-PD treatment. A macrolide-containing three-drug regimen is recommended over a two-drug regimen as a standard treatment, and azithromycin is recommended rather than clarithromycin. Both the 2007 and 2020 guidelines recommend a treatment duration of MAC-PD of at least one year after the culture conversion. Previous clinical studies have reported that ethambutol could prevent macrolide resistance. Furthermore, the concomitant use of aminoglycoside, amikacin liposomal inhalation, clofazimine, linezolid, bedaquiline, and fluoroquinolone with modification of guideline-based therapy has been studied.Long-term management of MAC-PD remains challenging because of the discontinuation of multi-drug regimens and the acquisition of macrolide resistance. Moreover, the poor compliance of guideline-based therapy for MAC-PD treatment worldwide is concerning since it causes macrolide resistance.Therefore, in this review, we focus on MAC-PD treatment and summarize various treatment options when standard treatment cannot be maintained, with reference to the latest ATS/ERS/ESCMID/IDSA clinical practice guidelines revised in 2020.     

Recurrence of idiopathic pulmonary hemosiderosis in adults with childhood onset: A case report and literature review

We describe a rare case of a 20-year-old Japanese man with idiopathic pulmonary hemosiderosis (IPH) recurrence in adults with childhood onset (racIPH). IPH commonly occurs in children, and data regarding racIPH are lacking. A review of the literature showed that only five cases of racIPH have been reported (including the present case) and that racIPH shows features that are intermediate between childhood- and adult-onset IPH with respect to age and a lower frequency of smoking history. We also found that the degree of anemia was usually not severe, and a favorable response to corticosteroid therapy is expected in racIPH.     

Database analysis of hypersensitivity pneumonitis in Japan

BackgroundThree epidemiological small-scale studies on hypersensitivity pneumonitis (HP) have been performed in Japan to date. Herein, we aimed to clarify the clinical characteristics of various types of HP diseases using a large nationwide database in Japan.MethodsWe used the Japanese Diagnostic Procedure Combination database that includes data from 1,031 participant hospitals. Patients with HP from 2011 to 2017 were identified using International Classification of Diseases 10th Revision codes. We analyzed patient characteristics, the yearly transition of the number of HP cases, rate per one million hospitalizations, geographical distribution, seasonality, and risk factors for in-hospital mortality.ResultsIn total, 3,634 patients with HP were identified, including summer-type HP (SHP) (n = 490), bird fancier's lung (BFL) (n = 199), ventilation pneumonitis (n = 106), farmer's lung (n = 48), and unspecified HP (n = 2761). The length of hospital stay was significantly longer in patients with BFL (19 days) than in patients with SHP (15 days). SHP was more prevalent in the southwestern region of Japan, and hospitalization occurred mainly in summer (37.8%) and fall (37.3%). Ventilation pneumonitis was predominant in winter (28.6%) and spring (38.7%). In-hospital mortality was significantly associated with old age (p < 0.001), low body mass index (p = 0.016), severe dyspnea (p < 0.001), and BFL diagnosis on admission (p = 0.031).ConclusionsThis study revealed the clinical characteristics of SHP and BFL, including the frequency of causative antigens, geographical distribution, seasonality, and risk factors for mortality, which may help in diagnosing HP and identifying causative antigens.     

Clinical features of idiopathic pleuroparenchymal fibroelastosis with progressive phenotype showing a decline in forced vital capacity

BackgroundIdiopathic pleuroparenchymal fibroelastosis (IPPFE) is heterogeneous, with some patients showing a progressive decline in forced vital capacity (FVC). However, the clinical features of these cases with progressive phenotypes remain unknown.MethodsThis retrospective study included 48 patients diagnosed with IPPFE who underwent longitudinal pulmonary function tests at our institution from 2005 to 2021. The progressive phenotype was defined as a relative decline of ≥10% in %FVC within two years from diagnosis of IPPFE, and its clinical features were evaluated.ResultsOf the 48 patients, 23 (47.9%) were classified as progressive IPPFE. They were significantly older with a higher rate of dyspnea, fine crackles on chest auscultation, lower-lobe usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography, and lower %FVC at diagnosis than non-progressive IPPFE. Additionally, progressive IPPFE had a significantly higher rate of long-term oxygen therapy requirement, the incidence of pneumothorax, and weight loss after diagnosis, which showed worse survival than non-progressive IPPFE. The relative decline in %FVC and weight loss showed a significant positive correlation. Multivariate analysis revealed that lower body mass index tended to predict early progression, and the coexistence of lower-lobe UIP pattern was significantly associated with early progression. A decline in %FVC was an independent poor prognostic factor in IPPFE.ConclusionsWith a progressive decline in %FVC, IPPFE often has an advanced stage at diagnosis and lower-lobe UIP pattern and is associated with weight loss and worse survival.