Risk Of Acute Exacerbation Research Articles

Short-term air pollution exposure and emergency department visits for amyotrophic lateral sclerosis: A time-stratified case-crossover analysis

BackgroundAmyotrophic lateral sclerosis (ALS) is a progressive and devastating neurodegenerative disease, eventually leading to respiratory failure. Although the only currently available therapeutic interventions merely slow the disease progression, few studies have examined risk factors associated with ALS exacerbation and progression. ObjectiveTo investigate the association between exposure to short-term air pollution and acute exacerbation of ALS requiring emergency department (ED) visit. MethodsWe identified from the national emergency database of Korea 617 patients who visited EDs in Seoul with ALS as a primary cause during the period 2008–2014. We estimated short-term exposure to particles <2.5 μm (PM2.5), particles <10 μm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and carbon monoxide (CO). We conducted a conditional logistic regression with a time-stratified case-crossover design to examine the association between ED visits for ALS and short-term exposure to interquartile range (IQR) increase and upper quartile levels of air pollutants on the day of the ED visit, compared to the control days matched to day of the week, month, and year. ResultsThe risk of ED visits for ALS was significantly associated with an IQR increase of PM2.5 [Odds ratio (OR) = 1.21; 95% confidence interval (CI): 1.08, 1.35], PM10 [OR = 1.13; 95% CI: 1.02, 1.25], SO2 [OR = 1.19; 95% CI: 1.01, 1.41], and CO [OR = 1.19; 95% CI: 1.03, 1.36]. Exposure to the highest quartiles of PM2.5 and PM10 showed higher associations with ED visits for ALS [OR = 1.40; 95% CI: 1.06, 1.85 and OR = 1.33; 95% CI: 1.00, 1.77]. DiscussionWe provide new evidence that exposure to short-term air pollution may increase the risk of acute exacerbation of ALS. Further studies are warranted to understand the underlying mechanisms.

Mucolytic Agents and Statins Use is Associated with a Lower Risk of Acute Exacerbations in Patients with Bronchiectasis-Chronic Obstructive Pulmonary Disease Overlap.

Background: Bronchiectasis-chronic obstructive pulmonary disease (COPD) overlap (BCO) is a neglected area of trials, and it is not covered by guidelines for clinical practice. Methods: Using the National Health Insurance Research Database of Taiwan, COPD patients with or without bronchiectasis from 2000 to 2009 were enrolled as the BCO and COPD alone cohorts, respectively. Patients followed for <28 days, diagnosed with COPD who were not prescribed with COPD medications, and those diagnosed with bronchiectasis who did not receive a chest X-ray or computed tomography were excluded. The primary endpoints were acute exacerbations and mortality. Results: There were 831 patients in the BCO cohort and 3321 patients in the COPD alone cohort, covering 3763.08 and 17,348.95 person-years, respectively, from 2000 to 2011. The BCO cohort had higher risk for exacerbations (adjusted hazard ratio (HR) 2.26, 95% confidence interval (CI) 1.94–2.63) and mortality (HR 1.46, 95% CI 1.24–1.73) than the COPD alone cohort. In the patients overall, the use of statins, macrolides, and mucolytic agents was associated with significantly lower risks of acute exacerbations (statins, HR 0.37, 95% CI 0.29–0.46; macrolides, HR 0.65, 95% CI 0.45–0.93; mucolytic agents, HR 0.68, 95% CI 0.59–0.78). Statins were associated with a significantly lower risk of mortality (HR 0.32, 95% CI 0.25–0.41). In the BCO group, statins and mucolytic agents use was associated with significantly lower risks of acute exacerbations (statins, HR 0.44, 95% CI 0.29–0.65; mucolytic agents, HR 0.58, 95% CI 0.45–0.75). Conclusion: Statins and mucolytic agents use may lower risk of acute exacerbation in patients with BCO.

Adesão à terapêutica nos doentes com esquizofrenia: uma revisão da literatura

Resumo: Introdução: Avaliar a adesão ao tratamento com agentes antipsicóticos em doentes com esquizofrenia é um desafio para qualquer médico psiquiatra, dada a subjetividade inerente ao tema. Apesar disso, a falta de adesão à terapêutica é prejudicial para o curso clínico da doença, resultando num risco aumentado de agudizações da doença e de internamentos hospitalares. O objetivo do presente estudo é rever a literatura corrente relativa aos fatores que influenciam a adesão ao tratamento antipsicótico em doentes com esquizofrenia. Métodos: Foi revista a literatura escrita em inglês entre 2006 e 2016 integralmente disponível no PubMed/MEDLINE que avaliasse potenciais fatores de risco para a adesão ao tratamento em doentes adultos (com mais de 18 anos) com esquizofrenia, através das palavras-chave: adherence, nonadherence, compliance, noncompliance, schizophrenia, psychosis, antipsychotic, neuroleptic. Resultados: Foram incluídos 39 estudos na revisão final. A média dos níveis de adesão ao tratamento foi de 32%. Foram identificados os seguintes fatores de risco para a falta de adesão ao tratamento: idade jovem, abuso de substâncias, psicopatologia psicótica presente, ausência de insight sobre a doença e a necessidade de tratamento, atitudes negativas perante o tratamento, relação médico-doente de má qualidade ou falta de apoio social e familiar. Conclusões: As intervenções direcionadas para melhorar a adesão à terapêutica devem ser individualizadas para cada doente, baseadas numa história clínica completa, para que todos os aspetos individuais que contribuam para esta variável possam ser convenientemente avaliados.

Chinese herbal medicine reduces acute hepatitis exacerbation in patients with hepatitis B virus infection: A case-control study in Taiwan

ObjectivesLittle information is available about the impact of Chinese herbal medicine (CHM) treatment on acute exacerbation of hepatitis. This study aimed to assess the risk of acute exacerbation of hepatitis and subsequent cirrhosis and hepatoma in HBV patients with and without CHM use. Design and settingThis population-based case-control study used data from the Taiwan Longitudinal Health Insurance Database from 2000 to 2013. Newly diagnosed HBV patients had acute exacerbation of hepatitis and subsequent cirrhosis and hepatoma as the case group, while another patients had no acute exacerbation of hepatitis and cirrhosis and hepatoma as the control group. To correct the differences in sociodemographic factors and Western medication use between the two groups, propensity score matching was used at a 1:1 ratio, and resulted in a comparison of 1306 and 805 patients per group, respectively. Main outcome measuresOccurrence of acute exacerbation of hepatitis and subsequent cirrhosis and hepatoma. ResultsOverall rate of acute exacerbation of hepatitis and subsequent cirrhosis and hepatoma was 7.9% and 4.8%, respectively. Patients receiving CHM had a significantly lower risk of acute exacerbation of hepatitis (adjusted odds ratio [aOR] =0.20, 95% confidence interval [95%CI]: 0.13–0.31) and subsequent cirrhosis and hepatoma (aOR = 0.29, 95%CI: 0.18–0.49) than those not receiving CHM after adjusting for relevant covariates. However, no dose-dependent relationship was exhibited for either incidence of acute exacerbation of hepatitis and cirrhosis and hepatoma. ConclusionThese findings highlight that the use of CHM was associated with a significantly reduced risk of acute exacerbation of hepatitis and subsequent cirrhosis and hepatoma in patients with HBV. Future research could further explore the benefit of CHM therapies for treatment of acute hepatitis exacerbation.

Modified risk scoring system for acute exacerbation of interstitial lung disease.

Lung cancer patients with interstitial lung disease often develop acute exacerbation of their interstitial lung disease after lung resection. Special care is needed in selection of the surgical procedure to reduce acute exacerbation and provide long-term survival. The Japanese Association for Chest Surgery devised a risk scoring system based on 7 risk factors to predict the probability of postoperative acute exacerbation. We excluded surgical procedures and used a modified system categorizing 4 groups: group A (risk score 0-6), group B (risk score 7-10), group C (risk score 11-14), and group D (risk score 15-18). We retrospectively examined 60 lung cancer patients with interstitial lung disease to determine whether the modified risk scoring system is useful for selecting the optimal surgical procedure in anticipation of curability and risk of postoperative acute exacerbation. Eight (13.3%) patients experienced postoperative acute exacerbation. In group A ( n = 20), there was no difference in the incidence of acute exacerbation between wedge (0%) and anatomic resection (6.3%, p = 0.800). In group B ( n = 40), the incidence was significantly higher after anatomic resection (5.0% vs. 30.0%, p = 0.046). Thus group A had high-quality outcomes with anatomic resection, and in group B, the incidence of postoperative acute exacerbation can be reduced if wedge resection is performed. Our modified risk scoring can be useful for selecting the optimal surgical procedure in anticipation of curability and the risk of acute exacerbation of interstitial lung disease after lung cancer surgery.

Elevated circulating MMP-9 is linked to increased COPD exacerbation risk in SPIROMICS and COPDGene.

Matrix metalloprotease 9 (MMP-9) is associated with inflammation and lung remodeling in chronic obstructive pulmonary disease (COPD). We hypothesized that elevated circulating MMP-9 represents a potentially novel biomarker that identifies a subset of individuals with COPD with an inflammatory phenotype who are at increased risk for acute exacerbation (AECOPD). We analyzed Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) and Genetic Epidemiology of COPD (COPDGene) cohorts for which baseline and prospective data were available. Elevated MMP-9 was defined based on >95th percentile plasma values from control (non-COPD) sample in SPIROMICS. COPD subjects were classified as having elevated or nonelevated MMP-9. Logistic, Poisson, and Kaplan-Meier analyses were used to identify associations with prospective AECOPD in both cohorts. Elevated MMP-9 was present in 95/1,053 (9%) of SPIROMICS and 41/140 (29%) of COPDGene participants with COPD. COPD subjects with elevated MMP-9 had a 13%-16% increased absolute risk for AECOPD and a higher median (interquartile range; IQR) annual AECOPD rate (0.33 [0-0.74] versus 0 [0-0.80] events/year and 0.9 [0.5-2] versus 0.5 [0-1.4] events/year for SPIROMICS and COPDGene, respectively). In adjusted models within each cohort, elevated MMP-9 was associated with increased odds (odds ratio [OR], 1.71; 95%CI, 1.00-2.90; and OR, 3.03; 95%CI, 1.02-9.01), frequency (incidence rate ratio [IRR], 1.45; 95%CI, 1.23-1.7; and IRR, 1.24; 95%CI, 1.03-1.49), and shorter time-to-first AECOPD (21.7 versus 31.7 months and 14 versus 21 months) in SPIROMICS and COPDGene, respectively. Elevated MMP-9 was independently associated with AECOPD risk in 2 well-characterized COPD cohorts. These findings provide evidence for MMP-9 as a prognostic biomarker and potential therapeutic target in COPD. ClinicalTrials.gov: NCT01969344 (SPIROMICS) and NCT00608764 (COPDGene). This work was funded by K08 HL123940 to JMW; R01HL124233 to PJC; Merit Review I01 CX000911 to JLC; R01 (R01HL102371, R01HL126596) and VA Merit (I01BX001756) to AG. SPIROMICS (Subpopulations and Intermediate Outcomes in COPD Study) is funded by contracts from the NHLBI (HHSN268200900013C, HHSN268200900014C,HHSN268200900015C HHSN268200900016C, HHSN268200900017C, HHSN268200900018C, HHSN268200900019C, and HHSN268200900020C) and a grant from the NIH/NHLBI (U01 HL137880), and supplemented by contributions made through the Foundation for the NIH and the COPD Foundation from AstraZeneca/MedImmune; Bayer; Bellerophon Therapeutics; Boehringer-Ingelheim Pharmaceuticals Inc.; Chiesi Farmaceutici; Forest Research Institute Inc.; GlaxoSmithKline; Grifols Therapeutics Inc.; Ikaria Inc.; Novartis Pharmaceuticals Corporation; Nycomed GmbH; ProterixBio; Regeneron Pharmaceuticals Inc.; Sanofi; Sunovion; Takeda Pharmaceutical Company; and Theravance Biopharma and Mylan. COPDGene is funded by the NHLBI (R01 HL089897 and R01 HL089856) and by the COPD Foundation through contributions made to an Industry Advisory Board composed of AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion.

Treatment of allergic rhinitis reduces acute asthma exacerbation risk among asthmatic children aged 2-18 years.

Asthma and allergic rhinitis (AR) frequently coexist in the same individuals in childhood and adolescence. We evaluated whether AR had an impact on acute exacerbation (AE) and whether intranasal corticosteroid (INCS) and second-generation antihistamines (SGH) for AR modified the association of AR with AE in asthmatics aged 2-6 years and 7-18 years. Using the National Health Research Institutes (NHRI) Database 2005 of Taiwan, we investigated patients who had been diagnosed with asthma in the years 2000 through 2012 and who had then been followed-up with for at least one year. The risk factors of AE were evaluated using multiple Cox proportional hazards regression analysis. The incidence of AE was higher in the preschool group than the older group (adj. HR: 1.68, 95% CI: 1.44-1.95). The AR with INCS and/or SGH group was found to have a lower risk of AE than the non-AR group (adj. HR: 0.32, 0.44 and 0.30), but the AR without treatment group did not have a significant difference with the non-AR group. After propensity score matching, the use of INCS and/or SGH was associated with a significant reduction in the occurrence of AE among AR patients aged 2-6 years old (adj. HR: 0.38, 0.57 and 0.45) and 7-18 years old (adj. HR: 0.50, 0.52 and 0.35). The preschool patients had a higher incidence of AE than the older patients in general. Adequate treatment with INCS and/or SGH in asthma with AR patients is important for reducing the incidence of AE of asthma.

New risk scoring system for predicting acute exacerbation of interstitial pneumonia after chemotherapy for lung cancer associated with interstitial pneumonia

BackgroundFatal acute exacerbation (AE) of interstitial pneumonia (IP) sometimes occurs after chemotherapy for lung cancer. We developed and evaluated a scoring system for assessing AE risk after chemotherapy in patients with lung cancer associated with IP. MethodsA review of medical records identified 109 patients with primary lung cancer associated with IP who had received chemotherapy at our center during the period from June 2007 through September 2017. We developed a model to score AE risk after chemotherapy in this patient group, and logistic regression was used to evaluate the model. ResultsThe anticancer agent score was determined by using AE rates reported in past studies. The risk score was calculated with the following formula: (1 × anticancer agent score) + (3 × smoking history [>70 pack-years]) + (4 × history of steroid use) + (3 × %diffusing capacity of lung carbon monoxide [<50%]). Patients were then classified into three groups. The AE incidence rate was 12% for a risk score of 0–5, 47% for a score of 6–10, and 66.7% for a score of ≥11. The sensitivity of the scoring system was 78.6% and specificity was 67.8%. ConclusionsThe present scoring system was able to identify IP patients at high risk for AE after chemotherapy for lung cancer associated with IP.

Blood eosinophilia, use of inhaled corticosteroids, and risk of COPD exacerbations and mortality.

PurposeIt remains unclear whether eosinophilia is useful for in guiding inhaled corticosteroid (ICS) therapy in chronic obstructive pulmonary disease (COPD) patients. The goal of this study is to evaluate the risk of acute exacerbations, COPD‐related hospitalisations/accident and emergency visits, and all‐cause mortality with various levels of eosinophil counts among COPD patients using ICS.MethodsA cohort study was conducted using the UK Clinical Practice Research Datalink. Patients were aged 40+ and had COPD (n = 32 693). Current users of ICS were stratified by relative and absolute eosinophil counts to determine the risk of outcomes with blood eosiniphilia using Cox regression analysis.ResultsAmong COPD patients, current use of ICS was not associated with a reduced risk of acute COPD exacerbations, COPD‐related hospitalisations/accident and emergency visits, and all‐cause mortality. Stratification of ICS use by absolute or relative eosinophil counts did not result in significant differences in risk of COPD exacerbations or hospitalisations/accident and emergency visits. However, all‐cause mortality was reduced by 12% to 24% among patients with eosinophilia.ConclusionsCOPD‐related acute exacerbations or hospitalisations/accident and emergency visits were not reduced with eosinophilia among users of ICS with COPD. However, all‐cause mortality was reduced by 12% to 24%. These findings are potentially important and require further evaluation in prospective studies.

Long noncoding RNAs antisense noncoding RNA in the INK4 locus (ANRIL) correlates with lower acute exacerbation risk, decreased inflammatory cytokines, and mild GOLD stage in patients with chronic obstructive pulmonary disease.

We aimed to assess the predictive value of long noncoding RNAs antisense noncoding RNA in the INK4 locus (lncRNAs ANRIL) for acute exacerbation of chronic obstructive pulmonary disease (COPD) and evaluate its correlation with inflammatory cytokines as well as the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage in COPD patients. A total of 136 acute exacerbations of COPD (AECOPD) patients, 138 stable COPD patients, and 140 healthy controls (HCs) were consecutively recruited, and plasma samples were collected. Real-time polymerase chain reaction was used to detect lncRNA ANRIL expression. Enzyme-linked immunosorbent assay was performed to detect inflammatory cytokines expressions. LncRNA ANRIL expression was lower in AECOPD patients compared with stable COPD patients and HCs (Both P < 0.001). Receiver operating characteristic curves revealed lncRNA ANRIL could distinguish AECOPD patients from HCs (area under curve (AUC):0.700, 95% CI: 0.638-0.762) and stable COPD patients (AUC: 0.659, 95% CI: 0.594-0.724). For inflammatory cytokines, lncRNA ANRIL expression was negatively correlated with TNF-α (P < 0.001), IL-1β (P = 0.015), IL-8 (P = 0.008), IL-17A (P = 0.002), and LTB-4 (P = 0.004) in AECOPD patients, while it was negatively correlated with TNF-α (P = 0.049), IL-1β (P = 0.005), IL-17A (P = 0.030), and LTB-4 (P = 0.011) in stable COPD patients. Furthermore, lncRNA ANRIL expression negatively correlated with GOLD stage in AECOPD patients (P = 0.001), but not in stable COPD patients (P = 0.131). LncRNA ANRIL associates with lower acute exacerbation risk, decreased inflammatory cytokines, and mild GOLD stage in COPD patients.

Survival after repeated surgery for lung cancer with idiopathic pulmonary fibrosis: a retrospective study

BackgroundPatients with idiopathic pulmonary fibrosis (IPF) have a high risk of developing lung cancer, but few studies have investigated the long-term outcomes of repeated surgery in such patients. The purpose of this study was to evaluate the surgical outcomes of repeated lung cancer surgery in patients with IPF.MethodsFrom January 2001 to December 2015, 108 lung cancer patients with IPF underwent pulmonary resection at two institutions; 13 of these patients underwent repeated surgery for lung cancer, and their data were reviewed.ResultsThe initial procedures of the 13 patients were lobectomy in 8, segmentectomy in 2, and wedge resection in 3. The subsequent procedures were wedge resection in 10 and segmentectomy in 3. The clinical stage of the second tumor was stage IA in 12 and stage IB in 1. Postoperatively, 3 patients (23.1%) developed acute exacerbation (AE) of IPF and died. The rate of decrease in percent vital capacity was significantly higher in patients with AE than in those without AE (p = 0.011). The 3-year overall survival rate was 34.6%. The causes of death were cancer-related in 7, AE of IPF in 3, and metachronous lung cancer in 1.ConclusionsDespite limited resection, a high incidence of AE was identified. The early and long-term outcomes of repeated surgery in lung cancer patients with IPF were poor because of the high risk of AE of IPF and lung cancer recurrence. Long-term intensive surveillance will be required to determine whether surgical intervention is justified in patients with multiple primary lung cancers and IPF.

Acute respiratory events in patients with bronchiectasis-COPD overlap syndrome: A population-based cohort study.

The clinical phenotypes of chronic obstructive pulmonary disease (COPD) are related to various outcomes. We investigated the risk of acute respiratory events in patients with bronchiectasis-COPD overlap syndrome (BCOS) in Taiwan. We included 3955 patients who received diagnoses of COPD and bronchiectasis from 2000 to 2007 from the Taiwan Longitudinal Health Insurance Database in the BCOS cohort. In the comparison cohort, we included patients with COPD but without bronchiectasis at a ratio of 4:1, frequency matched by age, sex, and index year with each patient with BCOS. We followed both cohorts for 5 years to investigate the incidence and risk of acute respiratory events in the BCOS cohort relative to the comparison cohort, the incidence rate ratios (IRRs) and corresponding 95% confidence intervals (CIs) were determined using Poisson regression models. The BCOS cohort experienced more episodes of acute respiratory events than did the comparison cohort (16.4 vs 5.52 per 100 person-y). After adjustment for potential covariates, the BCOS cohort had a 2.20-fold higher risk of pneumonia (adjusted IRR = 2.20, 95% CI = 2.06-2.34), a 3.88-fold higher risk of acute exacerbation (adjusted IRR = 3.88,95% CI = 3.64-4.13), a 1.74-fold higher risk of acute respiratory failure (adjusted IRR = 1.74,95% CI = 1.47-2.06), and a 1.99-fold higher risk of cardiopulmonary arrest (adjusted IRR = 1.99,95% CI = 1.81-2.20) than did the comparison cohort. The patients with BCOS had a higher risk of acute respiratory events than did COPD patients without bronchiectasis.

The associations between comorbidity and exacerbation risk in patients with chronic obstructive pulmonary disease

Objective: To study the association between comorbidity and acute exacerbation risk in patients with chronic obstructive pulmonary disease (COPD). Methods: This was a prospective cohort study with 64 stable COPD patients included. There were 64 males and 18 females with an average age of (68±9) years. Clinical characteristics, the number and type of comorbidities were recorded, and Charlson comorbidity index (CCI) was calculated. The patients were interviewed by phone calls every 3 months since baseline in which the number of acute exacerbations was recorded until 12 months. The impact of CCI, the number of comorbidities and certain comorbidities in the prediction of COPD exacerbation risk were analyzed. Results: Compared to patients with a lower CCI score, patients with a higher CCI score were older (75±6 vs 62±8), and had more severe lung function impairment [FEV(1)%pred: (40±18)% vs (52±18)% ], higher number of comorbidities [4(3, 7) vs 1(1, 3)] and higher frequency of hospital admission due to acute exacerbation [1(0, 2) vs 0(0, 0.25)]. In comparison with patients with lower number of comorbidities, patients with higher number of comorbidities were older (72±7 vs 64±10), and had higher mMRC score [2(1, 3) vs 2(1, 2)] and more severe lung function impairment [FEV(1)%pred: (42±15)% vs (53±19)% ], higher age adjusted CCI score [5(3, 5) vs 3(2, 3) ] and more courses of systemic corticosteroids [2(0, 3) vs 0(0, 0.75)] and/or antibiotics use [3(2, 4) vs 1.5(1, 2.75)]. The number of hospitalizations and total number of exacerbations were higher in COPD patients with bronchiectasis than those without (P<0.005). Conclusion: The inclusion of clinically meaningful comorbidities into the combined assessment of COPD for the prediction of disease prognosis deserves further study.

Chronic cough as a novel phenotype of chronic obstructive pulmonary disease.

Background and purposeChronic cough can be a dominant symptom of chronic obstructive pulmonary disease (COPD), although its clinical impact remains unclear. The aim of our study was to identify phenotypic differences according to the presence of chronic cough or sputum and evaluate the impact of chronic cough on the risk of acute exacerbation of COPD (AECOPD).MethodsIn a nationwide COPD cohort including 1,613 COPD patients, patients with chronic cough only, those with sputum only, those with chronic bronchitis (CB), and those without cough and sputum were compared with regard to dyspnea, lung function, quality of life (QoL), and risk of AECOPD.ResultsThe rates of chronic cough, chronic sputum, and both were 23.4%, 32.4%, and 18.2%, respectively. Compared with patients without chronic cough, those with chronic cough exhibited a lower forced expiratory volume in 1 second (% predicted) and diffusing capacity of the lungs for carbon monoxide (% predicted), more frequent AECOPD, more severe dyspnea, and worse QoL. Pulmonary function, dyspnea severity, and QoL worsened in the following order: without cough or sputum, with sputum only, with cough only, and with CB. Multivariate analyses revealed chronic cough as an independent risk factor for a lower lung function, more severe dyspnea, and a poor QoL. Moreover, the risk of future AECOPD was significantly associated with chronic cough (odds ratio 1.56, 95% CI 1.08–2.24), but not with chronic sputum.ConclusionOur results suggest that chronic cough should be considered as an important phenotype during the determination of high-risk groups of COPD patients.

Lower serum IgA is associated with COPD exacerbation risk in SPIROMICS.

BackgroundDecreased but measurable serum IgA levels (≤70 mg/dL) have been associated with risk for infections in some populations, but are unstudied in COPD. This study tested the hypothesis that subnormal serum IgA levels would be associated with exacerbation risk in COPD.MethodsData were analyzed from 1,049 COPD participants from the observational cohort study SPIROMICS (535 (51%) women; mean age 66.1 (SD 7.8), 338 (32%) current smokers) who had baseline serum IgA measured using the Myriad RBM biomarker discovery platform. Exacerbation data was collected prospectively (mean 944.3 (SD 281.3) days), and adjusted linear, logistic and zero-inflated negative binomial regressions were performed.ResultsMean IgA was 269.1 mg/dL (SD 150.9). One individual had deficient levels of serum IgA (<7 mg/dL) and 25 (2.4%) had IgA level ≤70 mg/dL. Participants with IgA ≤70 mg/dL were younger (62 vs. 66 years, p = 0.01) but otherwise similar to those with higher IgA. In adjusted models, IgA ≤70 mg/dL was associated with higher exacerbation incidence rates (IRR 1.71, 95% CI 1.01–2.87, p = 0.044) and greater risk for any severe exacerbation (OR 2.99, 95% CI 1.30–6.94, p = 0.010). In adjusted models among those in the lowest decile (<120 mg/dL), each 10 mg/dL decrement in IgA (analyzed continuously) was associated with more exacerbations during follow-up (β 0.24, 95% CI 0.017–0.46, p = 0.035).ConclusionsSubnormal serum IgA levels were associated with increased risk for acute exacerbations, supporting mildly impaired IgA levels as a contributing factor in COPD morbidity. Additionally, a dose-response relationship between lower serum IgA and number of exacerbations was found among individuals with serum IgA in the lowest decile, further supporting the link between serum IgA and exacerbation risk. Future COPD studies should more comprehensively characterize immune status to define the clinical relevance of these findings and their potential for therapeutic correction.

Distinctive characteristics and prognostic significance of interstitial pneumonia with autoimmune features in patients with chronic fibrosing interstitial pneumonia.

Interstitial lung diseases are heterogeneous, and patients with chronic fibrosing interstitial pneumonia (CFIP) often have clinical, serologic, and morphologic features suggestive but not diagnostic of connective tissue disease. Recently, the concept of interstitial pneumonia with autoimmune features (IPAF) has been proposed as a platform for such patients. However, the prognostic role of IPAF, including the cumulative incidence of acute exacerbations (AEs), is not fully clear. The aim of this study was to elucidate the clinical features and prognostic significance of IPAF. The clinical characteristics and prognostic relevance of a diagnosis of IPAF were retrospectively explored in 194 patients with CFIP, including 163 with idiopathic pulmonary fibrosis (IPF) and 31 with nonspecific interstitial pneumonia (NSIP), in our interstitial lung disease database. Sixteen percent of patients with CFIP (8% of IPF, 61% of NSIP) met the criteria for IPAF. Patients with IPAF were significantly younger and included a higher proportion of women, never-smokers, and patients with NSIP than those without IPAF. The morphologic domain was the most common in patients with IPAF (97%), followed by the serologic domain (72%) and clinical domain (53%). CFIP patients with IPAF had a more favorable prognosis with regard to overall survival (OS; P < 0.001, log-rank test) and incidence of AEs (P = 0.029, Gray's test) than those without IPAF. In the subgroup analysis, NSIP patients with IPAF had significantly better survival than those without IPAF (P = 0.031, log-rank test), and IPF patients with IPAF tended to have better OS than those without IPAF (P = 0.092, log-rank test). However, there were no significant differences in the incidence of AEs between patients with IPAF and those without IPAF in the IPF and NSIP subgroups. Furthermore, fulfilment of the IPAF criteria was an independent predictor of OS (hazard ratio (HR) 0.127; 95% confidence interval (CI) 0.017-0.952; P = 0.045) and incidence of AEs (HR 0.225: 95% CI 0.054-0.937; P = 0.040). A diagnosis of IPAF might predict a favorable prognosis and less risk of AEs in patients with CFIP.

Use of ICS/LABA Combinations or LAMA Is Associated with a Lower Risk of Acute Exacerbation in Patients with Coexistent COPD and Asthma

Based on current guidelines, more research is urgently needed to guide appropriate treatment for patients with asthma-chronic obstructive pulmonary disease (COPD) overlap. The objective of this study was to investigate medication effects on acute exacerbation in patients with coexistent COPD and asthma. Using Taiwan's National Health Insurance Research Database, we conducted a nationwide population-based study to evaluate medication effects in patients with COPD and asthma. Patients diagnosed with both asthma and COPD between 1997 and 2012 were enrolled as the COPD+ asthma cohort. The primary endpoint was acute exacerbation. The definitions of COPD and asthma were validated. The validation study confirmed the accuracy of definitions of COPD (86.2% sensitivity) and asthma (92.0% sensitivity). The study included 251,398 patients with COPD+ asthma and 514,522 patients with COPD alone, with a mean follow-up period of 9.85 years. After adjustment, hazard ratios (HRs) for long-acting muscarinic antagonist (LAMA) and inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) combinations were lower (time-dependent model, 1 year: LAMA, HR 0.51, 95% confidence interval [CI] 0.49-0.54; ICS/LABA combinations, HR 0.61, 95% CI 0.60-0.62; all P < .0001) than were those for LABAs or ICSs in patients with COPD and asthma. The use of LAMA or ICS/LABA combinations was associated with a lower risk of acute exacerbation in patients with COPD and asthma in this study.

Impact of Interstitial Lung Disease Classification on the Development of Acute Exacerbation of Interstitial Lung Disease and Prognosis in Patients with Stage III Non-Small-Cell Lung Cancer and Interstitial Lung Disease Treated With Chemoradiotherapy

Introduction: Data on the efficacy and risk of curative-intent chemoradiotherapy in patients with inoperable stage III non-small-cell lung cancer (NSCLC) and interstitial lung disease (ILD) are limited. The aim of this study was to explore the impact of ILD classification on acute exacerbation (AE) of ILD and prognosis in patients with stage III NSCLC and ILD treated with chemoradiotherapy.Materials and methods: We retrospectively reviewed the medical records of patients with stage III NSCLC and ILD treated with curative-intent chemoradiotherapy as the first-line treatment at the Shizuoka Cancer Center between June 2009 and May 2014.Results: Of 37 patients, 17 (46%) developed AE of ILD worse than grade 3 within 1 year after the last irradiation. In univariate analysis, the incidence rate of AE of ILD was lower in patients with a non-usual interstitial pneumonia (UIP) pattern than in those with a UIP pattern. Multivariate analysis showed that ILD classification was significantly associated with the incidence of AE of ILD. The median overall survival (OS) durations in patients with a non-UIP pattern and a UIP pattern were 16.5 and 9.3 months, respectively. In univariate analysis, patients with a non-UIP pattern showed better survival. Multivariate analysis showed that ILD classification was a significant independent prognostic factor.Conclusion: The incidence of AE of ILD was high in patients with stage III NSCLC and ILD treated with chemoradiotherapy as the first-line treatment. However, diagnosis of a non-UIP pattern could predict lower risk of AE of ILD and longer OS durations.

Efficacy and Safety of Nintedanib for the Treatment of Idiopathic Pulmonary Fibrosis: An Update.

Idiopathic pulmonary fibrosis is a fatal form of progressive fibrosing interstitial pneumonia with limited treatment options. In recent years, its management has been transformed with the approval of two new antifibrotic drugs: nintedanib and pirfenidone. Nintedanib is a tyrosine kinase inhibitor that efficiently slows idiopathic pulmonary fibrosis progression and has an acceptable tolerability profile. This article reviews new available evidence on the long-term efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis. Data from extension trials indicate that nintedanib continues to slow disease progression for up to 3 years and is similarly effective in patients with mild and severe impairment of lung function. Treatment with nintedanib reduces the risk of acute exacerbations, and a combined analysis of data from clinical trials of nintedanib shows a trend towards a reduction in mortality. Nintedanib is well tolerated and has been shown to be safe for up to 51 months. Gastrointestinal events, mainly diarrhoea, are the main adverse events caused by the treatment. Currently available data confirm its safety profile in real-life clinical settings, with no new safety concerns identified in patients with comorbidities.

A machine learning approach to triaging patients with chronic obstructive pulmonary disease.

COPD patients are burdened with a daily risk of acute exacerbation and loss of control, which could be mitigated by effective, on-demand decision support tools. In this study, we present a machine learning-based strategy for early detection of exacerbations and subsequent triage. Our application uses physician opinion in a statistically and clinically comprehensive set of patient cases to train a supervised prediction algorithm. The accuracy of the model is assessed against a panel of physicians each triaging identical cases in a representative patient validation set. Our results show that algorithm accuracy and safety indicators surpass all individual pulmonologists in both identifying exacerbations and predicting the consensus triage in a 101 case validation set. The algorithm is also the top performer in sensitivity, specificity, and ppv when predicting a patient’s need for emergency care.