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Aim: The efficacy and safety of pirfenidone have been previously demonstrated in patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF). However, the effect of pirfenidone in patients with advanced IPF remains unclear. Here, we investigated the effects of pirfenidone against advanced IPF in a real-world setting.Methods: A prospective nationwide post-marketing study was conducted on 258 patients from 10 Korean institutions. Patients with a predicted forced vital capacity (FVC) less than 50% or a diffusing capacity of the lung for carbon monoxide (DLco) less than 35% at baseline were classified as the advanced IPF group.Results: Of 219 patients included in the analysis, the majority were male (76.3%); the mean age was 67.3 years, and the advanced group accounted for 17.8% of the patients. The median treatment duration was 298 days. Among the subjects, 86.3% experienced adverse events (AEs), of which a decreased appetite (32.4%) and a photosensitivity reaction (13.7%) were the most frequent. The incidence of AEs was similar between the advanced and non-advanced groups (92.3% vs. 85.0%, respectively; p = 0.229). Although the overall discontinuation rate was higher in the advanced group than in the non-advanced group (74.4% vs. 50.0%, respectively; p = 0.006), the percentages of the patients who discontinued treatment as a result of AEs were similar in both groups (20.5% vs. 23.3%, respectively; p = 0.704). In all patients, the rates of decline in the predicted FVC and DLco over 48 weeks were - 4.3 ± 1.3% and - 4.4 ± 1.7%, respectively. There was no between-group difference in the rate of lung function decline.Conclusions: Pirfenidone used for the treatment of patients with IPF in a real-world setting was well tolerated, with an acceptable safety profile and a consistent therapeutic effect, regardless of the disease severity.Trial Registration: ClinicalTrials.gov NCT03761082; the trial was retrospectively registered on December 3, 2018. [ABSTRACT FROM AUTHOR]

Background: Innate T helper type 2 (Th2) immune responses mediated by interleukin (IL)-33, thymic stromal lymphopoietin (TSLP), and IL-25 have been shown to play an important role in pulmonary fibrosis of animal models; however, their clinical implications remain poorly understood.Methods: TSLP, IL-25, and IL-33 concentrations were measured in bronchoalveolar lavage fluids obtained from normal controls (NCs; n = 40) and from patients with idiopathic pulmonary fibrosis (IPF; n = 100), non-specific interstitial pneumonia (NSIP; n = 22), hypersensitivity pneumonitis (HP; n = 20), and sarcoidosis (n = 19).Results: The TSLP and IL-33 levels were significantly higher in patients with IPF relative to the NCs (p = 0.01 and p = 0.0001, respectively), NSIP (p = 4.95E - 7 and p = 0.0002, respectively), HP (p = 0.00003 and p = 0.000005, respectively), and sarcoidosis groups (p = 0.003 and p = 0.0001, respectively). However, the IL-25 levels were not significantly different between NC and IPF group (p = 0.432). Receiver operating characteristic curves of the TSLP and IL-33 levels revealed clear differences between the IPF and NC groups (AUC = 0.655 and 0.706, respectively), as well as between the IPF and the other lung disease groups (AUC = 0.786 and 0.781, respectively). Cut-off values of 3.52 pg/μg TSLP and 3.77 pg/μg IL-33 were shown to differentiate between the IPF and NC groups with 99.2 and 94.3% accuracy. Cut-off values of 4.66 pg/μg TSLP and 2.52 pg/μg IL-33 possessed 99.4 and 93.2% accuracy for differentiating among the IPF and other interstitial lung disease groups.Conclusions: Innate immune responses may be associated with the development of IPF. Furthermore, the IL-33 and TSLP levels in BAL fluids may be useful for differentiating IPF from other chronic interstitial lung diseases. [ABSTRACT FROM AUTHOR]

Objective. According to the American Thoracic Society, approximately 5% of all asthmatics have refractory asthma (RA); these patients fail to recover lost lung function even after long-term treatment with high doses of medications. Methods. Using a time-trend controlled case-crossover study design, we calculated odds ratios to evaluate whether exposure to ambient air pollutants and certain meteorological conditions on the day of admission (Lag 0) and up to 3 days before admission (Lag1 through Lag 3) were associated with acute RA exacerbation. Results were obtained after controlling for the effects of seasonality, smoking, and allergen sensitivity; we stratified our data into four seasons with respect to the median temperature of each month and further stratified them according to self-reported smoking status and skin-prick test results. Results. In our study, RA patients ( n = 82), living in metropolitan city of Seoul and Kyunggi Province, accounted for 3.7% of all asthmatics ( n = 2298) registered in our asthma cohort between 2005 and 2009. In winter, a 1°C decrease in ambient temperature and a 1 ppb increase in sulfur dioxide concentration on the day of Lag 1 were associated with 14.8% (95% confidence interval [CI]: 0.9-26.7) and 19.7% (95% CI: 3.3-38.7) increases in the risk of RA exacerbation among nonsmokers, respectively. Similar associations were obtained on the day of Lag 2. The association remained unchanged after excluding patients sensitive to Dermatophagoides farinae and Dermatophagoides pteronyssinus. Conclusions. Exposure to temperature drops and increased sulfur dioxide concentrations are positively associated with the occurrence of acute RA exacerbation during winter with 1 or 2 day lags. [ABSTRACT FROM AUTHOR]

Background: Nasal polyps are abnormal lesions that cause airway obstruction and can occur along with other respiratory diseases. On account of its association with aspirin exacerbated respiratory disease (AERD), the human discoidin, CUB and LCCL domain containing 2 ( DCBLD2) is hypothesized to be a candidate gene for the development of nasal polyps in asthma patients. Methods: A total of 12 single-nucleotide polymorphisms (SNPs) were genotyped in 467 Korean asthma patients who were stratified further into 108 AERD and 353 aspirin-tolerant asthma (ATA) subgroups. Five major haplotypes were inferred from pairwise comparison of the polymorphisms. The patients were matched to control for confounds, and differences in the frequency distribution of DCBLD2 SNPs and haplotypes were analyzed using logistic models via various modes of genetic inheritance. Results: Results reveal significant association of rs828618 and DCBLD2_ht1 with nasal polyposis in the overall asthma patients group ( P = 0.006, P = 0.05). Interestingly, the strength of association were maintained in the ATA subgroup ( P = 0.007, P = 0.06), and moderate correlation was detected in the AERD subgroup ( P = 0.04-0.05, P > 0.05). Conclusions: Although further replication and validation are needed, these findings suggest that DCBLD2 could be a potential marker and drug target for treatment of nasal polyposis in Korean asthma patients. [ABSTRACT FROM AUTHOR]