Prevalence of pulmonary embolism in patients with obstructive sleep apnea and chronic obstructive pulmonary disease: The overlap syndrome

ObjectiveGrowing evidence indicates that both obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) may be closely associated with the prevalence of pulmonary embolism (PE). However, the relationship of overlap syndrome (OS) (coexistence of OSA and COPD) with PE is unclear. The purpose of this study was to investigate whether OS were associated with increased PE prevalence.MethodsWe performed a retrospective chart review of patients who underwent sleep study at Beijing An Zhen Hospital from 2011 to 2014. The association of OS with PE prevalence was estimated by using logistic regression models.ResultsIn contrast to control patients (neither OSA nor COPD), those subjects with OS had higher odds of PE (OR9.61; 95%CI 4.02–21.31, p < 0.001) with significance persisting after adjusting for covariates (OR 5.66; 95%CI 1.80–16.18, p = 0.004). Meanwhile, patients with OS compared with those with isolated OSA also had significantly higher odds of PE in univariate (OR 4.79; 95%CI 2.04–10.33, p = 0.0007) and adjusted models (OR 3.89; 95%CI 1.27–10.68, p = 0.019). In subgroup analysis, patients with OS had higher odds of PE than control group among male subjects (OR 8.12, 95%CI1.86–31.87, p = 0.007) and patients ≥ 58years (OR 5.50, 95%CI 1.51–18.14, p = 0.012) in multivariable models. Percentage of total sleep time with saturation lower than 90% (T90) ≥ 2.6% was significantly associated with prevalence of PE (OR 4.72, 95%CI1.34–19.83, p = 0.015) in subgroup of patients older than 58.ConclusionsOS is independently associated with PE prevalence. Longitudinal studies are needed to better understand the relationship with incident PE.     

Blood eosinophil count variability in chronic obstructive pulmonary disease and severe asthma

BackgroundBlood eosinophils are essential biomarkers that vary substantially over time in patients with COPD and asthma. However, no study has identified the changes and effects in the changes of the blood eosinophil counts over time in both diseases. This study aimed to demonstrate blood eosinophil variability in patients with COPD and severe asthma based on these backgrounds.MethodsA total of 172 patients with COPD from the Hokkaido COPD cohort study and 96 patients with severe asthma from the Hokkaido Severe Asthma Cohort Study, whose blood eosinophil counts were measured annually over a 3-year period, were analyzed. The factors contributing to consistently high or low blood eosinophil counts were examined in each cohort. The stability of the eosinophil classification (<150, 150–299, ≥300 cells/μL) was compared based on the number of asthma-like features in patients with COPD and the smoking status in patients with severe asthma.ResultsAmong all the patients, the most stable range of baseline blood eosinophil counts differed between the two diseases, with <150 cells/μL in COPD and ≥300 cells/μL in severe asthma. In COPD, the number of asthma-like features (bronchodilator reversibility, blood eosinophilia, and atopy) affects the blood eosinophil count variation patterns. In severe asthma, smoking status did not affect the blood eosinophil count variation patterns.ConclusionsWe identified variations in the blood eosinophil counts and their contributing factors in patients with COPD and severe asthma.     

Quantitative computed tomography-based evaluation of skeletal muscle and presence of sarcopenia in patients with chronic obstructive pulmonary disease

Sarcopenia, or age-related muscle loss, is a common comorbidity in patients with chronic obstructive pulmonary disease (COPD) with multiple contributing factors. We hypothesized that the presence of sarcopenia can be estimated using quantitative computed tomography-based parameters in patients with COPD. We retrospectively evaluated 38 elderly (≥65 years) men with COPD for pooled data, including hand grip strength and gait speed. Sarcopenia was diagnosed based on the updated 2019 criteria set by the Asian Working Group for Sarcopenia. Cross-sectional area of the erector spinae muscle (ESM) and pectoralis muscle (PM) were quantitatively evaluated and adjusted by height (ESM-I, and PM-I). Sarcopenia was diagnosed in 11 (29%) patients. The mean ESM-I and PM-I were 11.0 and 9.5 cm²/m², respectively, and significantly correlated with height-adjusted appendicular skeletal muscle mass. The optimal cutoff ESM-I for the presence of sarcopenia was 9.41 cm²/m². ESM loss helped estimate sarcopenia in patients with COPD.     

Association between low mean corpuscular hemoglobin and prognosis in patients with exacerbation of chronic obstructive pulmonary disease

BackgroundSeveral studies have demonstrated the association between mean corpuscular hemoglobin concentration (MCHC), a hematological index used for the assessment of anemia, and the prognosis of patients with heart disease. While the red cell distribution width (RDW) is known to be related to the prognosis of patients with chronic obstructive pulmonary disease (COPD), few studies have focused on the association between the MCHC and COPD. Therefore, we examined the association between the MCHC and prognosis in patients with exacerbation of COPD.MethodsWe examined the association between the 30-day mortality and clinical findings in patients with COPD exacerbation who were hospitalized between October 2008 and December 2018.ResultsWe enrolled 195 patients with COPD exacerbation (average age: 76.4 years; 181 men, 14 women). The MCHC was significantly lower, while the RDW was significantly higher in the 27 patients (13.8%) who died during the 30-day observation period compared to those in the patients who survived. Multivariate logistic regression analysis revealed that the MCHC was independently associated with 30-day mortality. The area under the curve calculated from the MCHC obtained from peripheral blood was 0.688 and the cutoff value was 31.6 g/dL, with a sensitivity of 0.593 and specificity of 0.810 (p = 0.0001).ConclusionThe MCHC might be a valuable biomarker for evaluating the prognosis of patients with COPD exacerbation.     

Lobar distribution of non-emphysematous gas trapping and lung hyperinflation in chronic obstructive pulmonary disease

BackgroundLung hyperinflation in chronic obstructive pulmonary disease (COPD) is closely associated with emphysema and non-emphysematous gas trapping, termed functional small airway disease (fSAD), on inspiratory and expiratory computed tomography (CT). Because the cranial-caudal emphysema distribution affects pulmonary function and fSAD may precede emphysema on CT, we tested the hypothesis that lobar fSAD distribution would affect lung hyperinflation differently in COPD with minimal and established emphysema.MethodsThe volume percentages of fSAD and emphysema (fSAD% and Emph%) over the upper and lower lobes were measured using inspiratory and expiratory CT in 70 subjects with COPD. Subjects were divided into those with minimal and established emphysema (n = 36 and 34) using a threshold of 10% Emph% in the whole lung.ResultsIn the minimal emphysema group, fSAD% in the upper and lower lobes was positively correlated with functional residual capacity (FRC) and residual volume to total lung capacity ratio (RV/TLC), and the correlation of fSAD% with RV/TLC was greater in the lower lobes. Conversely, in the established emphysema group, fSAD% in the upper and lower lobes was correlated with RV/TLC, but not with FRC. In multivariate analysis, fSAD% in the lower lobes, but not in the upper lobes, was associated with RV/TLC in subjects with minimal emphysema after adjusting for age, smoking status, and bronchodilator use.ConclusionNon-emphysematous gas trapping in the upper and lower lobes has a distinct physiological effect, especially in COPD with minimal emphysema. This local evaluation might allow sensitive detection of changes in lung hyperinflation in COPD.     

Correlation of 4-meter gait speed with clinical indicators of chronic obstructive pulmonary disease

BackgroundMeasuring daily physical activity and exercise capacity is recommended in the routine care of patients with chronic obstructive pulmonary disease (COPD). The 4-m gait speed (4mGS) is simple and effective in stratifying patients according to exercise performance, dyspnea, health status, and prognosis. We assessed the reliability of the 4mGS as a clinical marker by examining its association with established clinical indicators among hospitalized patients with COPD.MethodsThis retrospective study included 78 patients hospitalized with COPD (mean age: 76.3 ± 0.9 years; males, n = 69) between January 2016 and June 2018 who were assessed using the 4mGS and divided into slow (<0.8 m/s) and normal (≥0.8 m/s) 4mGS groups. Clinical characteristics were compared, including death during the observation period, time to first exacerbation, and long-term oxygen therapy requirement.ResultsThere were strong relationships between 4mGS performance, the 6-min walk test (R = 0.70; p < 0.0001), and the modified Medical Research Council dyspnea scale (R = 0.68; p < 0.0001) among the 78 patients. The slow 4mGS group had a higher frequency of death during the observation period (p = 0.0095) and a greater requirement for long-term oxygen therapy (p = 0.0063). The 4mGS correlated with inspiratory capacity (IC) and IC/total lung capacity ratios, which are respiratory failure indicators.ConclusionsThe 4mGS is a simple and easy method of assessing the physical condition as well as estimating the prognosis of patients with COPD, and may serve as a useful marker in home medical treatment or clinical settings.     

Increased LHX9 expression in alveolar epithelial type 2 cells of patients with chronic obstructive pulmonary disease

BackgroundAlveolar epithelial type 2 (AT2) cells serve as stem cells in alveolar epithelium and are assumed to lose their stem cell function in the lungs of chronic obstructive pulmonary disease (COPD). Although we previously reported that LHX9 mRNA expression was up-regulated in AT2 cells of COPD lung tissues, it is yet to be elucidated how LHX9 is associated with the vulnerability of AT2 cells in COPD.MethodsAT2 cells were isolated from lung tissues of 10 non-COPD subjects and 11 COPD patients. LHX9 mRNA expression was determined by quantitative RT-PCR. To identify up-stream molecules, an alveolar epithelial cell line A549 was exposed to pro-inflammatory cytokines in vitro. siRNA-mediated Lhx9 knockdown was performed to determine how Lhx9 affected the cellular viability and the cell-division cycle.ResultsLHX9 mRNA expression was increased in AT2 cells from COPD lung tissues, compared to those from non-COPD tissues. The airflow obstruction was independently correlated with the increase in LHX9 expression. Among several pro-inflammatory cytokines, interferon-γ was a strong inducer of LHX9 expression in A549 cells. Lhx9 was involved in the increased susceptibility to serum starvation-induced death of A549 cells.ConclusionsOur data suggest that IFN-γ predominantly increases the LHX9 expression which enhances the susceptibility to cell death. Considering the independent association of the increased LHX9 expression in AT2 cells with airflow obstruction, the IFN-γ-Lhx9 axis might contribute to the vulnerability of AT2 cells in the lungs of COPD patients.     

Cellular senescence—an aging hallmark in chronic obstructive pulmonary disease pathogenesis

Chronic obstructive pulmonary disease (COPD),¹ a representative aging-related pulmonary disorder, is mainly caused by cigarette smoke (CS) exposure. Age is one of the most important risk factors for COPD development, and increased cellular senescence in tissues and organs is a component of aging. CS exposure can induce cellular senescence, as characterized by irreversible growth arrest and aberrant cytokine secretion of the senescence-associated secretory phenotype; thus, accumulation of senescent cells is widely implicated in COPD pathogenesis. CS-induced oxidative modifications to cellular components may be causally linked to accelerated cellular senescence, especially during accumulation of damaged macromolecules. Autophagy is a conserved mechanism whereby cytoplasmic components are sent for lysosomal degradation to maintain proteostasis. Autophagy diminishes with age, and loss of proteostasis is one of the hallmarks of aging. We have reported the involvement of insufficient autophagy in regulating CS-induced cellular senescence with respect to COPD pathogenesis. However, the role of autophagy in COPD pathogenesis can vary based on levels of cell stress and type of selective autophagy because excessive activation of autophagy can be responsible for inducing regulated cell death. Senotherapies targeting cellular senescence may be effective COPD treatments. Autophagy activation could be a promising sonotherapeutic approach, but the optimal modality of autophagy activation should be examined in future studies.     

Exhaled nitric oxide: A biomarker for chronic obstructive pulmonary disease

The fractional concentration of exhaled nitric oxide (FeNO) is recognized as a biomarker of type 2 inflammation in asthma, which is related to airway eosinophilia. We conducted a prospective observational study in a cohort of Japanese patients with chronic obstructive pulmonary disease (COPD) to evaluate the relationship between FeNO and clinical features and patient outcomes over a 3-year period. Participants were categorized into two groups based on FeNO levels (high and low), and the clinical features and outcomes were compared between the groups. Patients with high FeNO levels showed features of asthma and eosinophilic inflammation compared to those with low levels. However, high FeNO levels were not associated with worse outcomes (exacerbations, hospital admissions, all-cause and disease-specific mortality) compared to low levels. These results provide evidence that baseline FeNO is related to eosinophilic inflammation; however, is not a predictor of future exacerbations or prognosis in patients with stable COPD.     

Hydrogen sulfide as a novel biomarker of asthma and chronic obstructive pulmonary disease

Hydrogen sulfide (H₂S) has recently been recognised as the third important gas-signalling molecule, besides nitric oxide and carbon monoxide. H₂S has been reported to be produced by many cell types in mammalian tissues and organs throughout the actions of H₂S-generating enzymes or redox reactions between the oxidation of glucose and element of sulfur. Although the pathological role of H₂S has not yet been fully elucidated, accumulative data suggest that H₂S may have biphasic effects. Briefly, it mainly has anti-inflammatory and antioxidant roles, although it can also have pro-inflammatory effects under certain conditions where rapid release of H₂S in tissues occur, such as sepsis. To date, there have been several clinical studies published on H₂S in respiratory disorders, including asthma and chronic obstructive pulmonary disease (COPD). According to previous studies, H₂S is detectable in serum, sputum, and exhaled breath, although a gold standard method for detection has not yet been established. In asthma and COPD, H₂S levels in serum and sputum can vary depending on the underlying conditions such as an acute exacerbation. Furthermore, sputum H₂S in particular correlates with sputum neutrophils and the degree of airflow limitation, indicating that H₂S has potential as a novel promising biomarker for neutrophilic airway inflammation for predicting current control state as well as future risks of asthma. In the future, concurrent measures of H₂S with conventional inflammatory biomarkers (fractional exhaled nitric oxide, eosinophils etc) may provide more useful information regarding the identification of inflammatory phenotypes of asthma and COPD for personalised treatment.     

The efficacy of mass screening for chronic obstructive pulmonary disease using screening questionnaires in a medical health check-up population

BackgroundChronic obstructive pulmonary disease (COPD) is a preventable and treatable disease, highlighting the need for efficient screening strategies to identify patients with COPD. However, there is little evidence regarding the efficacy of mass screening for COPD, and no epidemiological studies on COPD have been conducted in the Shikoku region of Japan.MethodsIn this cross-sectional study, we originally investigated the efficacy of mass screening for COPD among community residents in the aforementioned region using two COPD screening questionnaires.ResultsFrom July 2018 through January 2019, 688 participants were enrolled. COPD was diagnosed using the Global Initiative for the Chronic Obstructive Lung Disease criteria. Twenty-one patients were newly diagnosed with COPD and 19 (90.5%) had early stages COPD. The prevalence of COPD in this study was 3.1%. The COPD Population Screener (COPD-PS) questionnaire and the International Primary Care Airways Guidelines (IPAG) questionnaire had extremely high negative predictive values in discriminating participants with COPD from those without. The scores of both questionnaires were correlated with spirometric tests and with each other. The COPD-PS questionnaire had significantly better specificity and area under the receiver operating characteristic curve value than the IPAG questionnaire. Moreover, only the COPD-PS questionnaire was identified as an independent factor for predicting COPD diagnosis in the multivariate analysis.Conclusions: Mass screening for COPD using screening questionnaires, particularly the COPD-PS questionnaire, might be useful to identify the early stages of COPD in a medical health check-up population.     

Treatment efficacy of LAMA versus placebo for stable chronic obstructive pulmonary disease: A systematic review and meta-analysis

BackgroundFour long-acting muscarinic antagonists (LAMAs), tiotropium, glycopyrronium, aclidinium, and umeclidinium, are currently available for the treatment of stable chronic obstructive pulmonary disease (COPD). However, no integrated analysis has sought to determine the effectiveness of these LAMAs. Thus, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of LAMA versus placebo in patients with stable COPD.MethodsA literature search of relevant randomized control trials that administered LAMA to stable COPD patients was conducted, and the exacerbations, quality of life (QoL), dyspnea score, lung function, and adverse event of patients were evaluated.ResultsA total of 33 studies were included in this meta-analysis. LAMA significantly decreased the frequency of exacerbations compared to the placebo (OR 0.75; 95% CI 0.66 to 0.85; P < 0.001). The mean changes in the St George's Respiratory Questionnaire score (mean difference, ?3.61; 95% CI, ?4.27 to ?2.95; P < 0.00001), transitional dyspnea index score (mean difference 1.00; 95% CI 0.83 to 1.17; P < 0.00001), and trough FEV₁ (mean difference 0.12; 95% CI 0.11 to 0.13; P < 0.0001) indicated significantly greater improvement in the LAMA group than the placebo group. The number of withdrawals due to adverse events in the LAMA group was significantly fewer than that in the placebo group (OR -0.02; 95% CI -0.03 to ?0.01; P = 0.002).ConclusionLAMA is superior to placebo due to lower frequency of exacerbations and adverse events, as well as higher trough FEV₁, QoL, and dyspnea score for stable COPD.     

Real-life long-term safety and effectiveness of omalizumab in Japanese pediatric patients with severe allergic asthma: A post-marketing surveillance

BackgroundOmalizumab is approved as add-on therapy for pediatric asthma since 2013 in Japan, however, its data in clinical practice is limited. This post-marketing surveillance aimed to evaluate long-term safety and effectiveness of omalizumab in Japanese pediatric patients with severe allergic asthma in real-life setting.MethodsThis 104-week, multicenter surveillance was conducted from September 2013 to May 2019 by central registration method. Patients with severe allergic asthma aged ≥6 and < 15 years at initiation of treatment who were first-time omalizumab users were included. The primary endpoints included incidence of adverse drug reactions and physician's Global Evaluation of Treatment Effectiveness (GETE). The secondary endpoints included incidence of serious adverse events, adverse events and adverse drug reactions of special interest and asthma exacerbation-related events.ResultsOf the 128 patients enrolled, 127 completed the surveillance and were included for safety and effectiveness analysis. Thirteen patients experienced 20 adverse drug reactions with an incidence rate of 10.2%. The most frequent adverse drug reactions were pyrexia (2.4%) and urticaria (1.6%). In total, adverse events and serious adverse events occurred in 60 (47.2%) and 30 patients (23.6%) respectively. Two patients experienced anaphylactic reaction and 1 patient experienced type 1 hypersensitivity. 77.2% had an effective response to omalizumab according to GETE at final assessment, and frequency of all asthma exacerbation-related events decreased in post-treatment versus pre-treatment.ConclusionsLong-term omalizumab treatment showed no new safety signals in pediatric patients with severe allergic asthma. The observed safety and effectiveness profile was consistent with previous studies.     

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.     

Two cases of chronic obstructive pulmonary disease with undetectable diffusing capacity for carbon monoxide

Pulmonary diffusing capacity for carbon monoxide (DL_CO) is a valuable pulmonary function test to evaluate the gas exchange capacity of the lungs. Generally, DL_CO values are significantly lower in patients with chronic obstructive pulmonary disease (COPD), particularly in those with a predominantly emphysema phenotype. However, it is extremely rare that DL_CO values cannot be obtained for reasons other than technical errors. Herein, we report two patients with COPD in whom DL_CO values were undetectable without prolonging the breath-holding time for the test. We discuss possible mechanisms for these peculiar findings.     

Two cases of chronic obstructive pulmonary disease evaluated by dynamic-ventilatory digital radiography for pulmonary function and assessment of treatment efficacy

Spirometry is a crucial test used in the diagnosis and monitoring of patients with chronic obstructive pulmonary disease (COPD). Severe acute respiratory syndrome coronavirus 2 pandemic has posed numerous challenges in performing spirometry. Dynamic-ventilatory digital radiography (DR) provides sequential chest radiography images during respiration with lower doses of radiation than conventional X-ray fluoroscopy and computed tomography. Recent studies revealed that parameters obtained from dynamic DR are promising for evaluating pulmonary function of COPD patients. We report two cases of COPD evaluated by dynamic-ventilatory DR for pulmonary function and treatment efficacy and discuss the potential of dynamic DR for evaluating COPD therapy.     

Efficacy and safety of pemafibrate in patients with hypertriglyceridemia in clinical settings: A retrospective study

Background and aimsRecently, pemafibrate, a selective PPARα modulator, has been developed as a treatment for hypertriglyceridemia and has attracted much attention. The aims of this study were to evaluate the efficacy and safety of pemafibrate in hypertriglyceridemia patients under clinical settings.Methods and resultsWe evaluated changes in lipid profiles and various parameters before and after 24-week pemafibrate administration in patients with hypertriglyceridemia who had not previously taken fibrate medications. There were 79 cases included in the analysis. 24 weeks after the treatment with pemafibrate, TG was significantly reduced from 312 ± 226 to 167 ± 94 mg/dL. In addition, lipoprotein fractionation tests using PAGE method showed a significant decrease in the ratio of VLDL and remnant fractionations, which are TG-rich lipoproteins. After pemafibrate administration, body weight, HbA1c, eGFR, and CK levels were not changed, but liver injury indices such as ALT, AST, and γ-GTP were significantly improved.ConclusionIn this study, pemafibrate improved the metabolism of atherosclerosis-induced lipoproteins in hypertriglyceridemia patients. In addition, it showed no off-target effects such as hepatic and renal damage or rhabdomyolysis.     

Prevalence,disease burden,and treatment reality of patients with severe,uncontrolled asthma in Japan

BackgroundThe severe asthma and severe, uncontrolled asthma (SUA) populations in Japan are not well-studied. We investigated the prevalence of continuously treated severe asthma and SUA patients, their disease burden, and the treatment reality via a Japanese health insurance claims database.MethodsContinuously treated asthma patients (patients prescribed inhaled corticosteroids for asthma ≥4 times in the past year) aged ≥17 years at the index date (latest visit between April 2014 and March 2015 for asthma treatment) were included in this analysis (KEIFU study, UMIN000027695). Asthma severity and control status at the index date were defined using modified criteria of ERS/ATS guidelines. Asthma hospitalization, oral corticosteroid (OCS) use, and total medical expenses were calculated using data up to 12 months post–index date.ResultsWe identified 10,579 patients as continuously treated asthma patients. Of these, 823 (7.8%) had severe asthma; 267 (2.5%) and 556 (5.3%) patients had SUA and severe, controlled asthma (SCA), respectively. Compared with SCA and mild to moderate asthma patients, a greater percentage of SUA patients required hospitalization (13.7%, 6.2%, and 3.0%, respectively) and were prescribed OCSs (67.4%, 45.9%, and 16.2%, respectively). Yearly total medical expenses were also greater for SUA patients (mean [standard deviation]: 8346 [12,280], vs 5989 [10,483] and 3422 [8800] USD, respectively).ConclusionsThe percentages of severe asthma and SUA patients continuously treated in Japan were obtained through this large-scale analysis using a health insurance claims database. SUA patients had greater medical and economic burdens, suggesting more appropriate treatment is required according to the treatment guidelines.     

Differences in the spectrum of respiratory viruses and detection of human rhinovirus C in exacerbations of adult asthma and chronic obstructive pulmonary disease

BackgroundViral respiratory infections are a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and asthma. We conducted a multicenter prospective study to determine the differences in the spectrum of viruses between adults with asthma exacerbations and AECOPD and assessed the prevalence and impact of human rhinovirus (HRV)-C in adults, which is more pathogenic in children with asthma than other HRV species.MethodsNasopharyngeal and serum samples and clinical information were collected from 64 outpatients with adult asthma exacerbations and 44 outpatients with AECOPD between April 2018 and March 2020. Viral pathogens and HRV strains were identified from nasal samples by multiplex PCR and VP4/VP2 nested PCR.ResultsViral pathogens were identified in 31 patients with asthma exacerbations (48.4%) and 17 patients with AECOPD (38.6%). The most commonly detected viruses were HRV/enterovirus followed by human metapneumovirus (hMPV) in patients with asthma exacerbations, and hMPV followed by parainfluenza virus in patients with AECOPD. HRV-C was the HRV species most commonly associated with both asthma exacerbations and AECOPD. Clinical characteristics, baseline lung function, serum inflammatory chemokines, hospitalization, and systemic steroid use did not differ between HRV-C-positive patients and those positive for other HRV species.ConclusionsExacerbation-associated spectrum of viruses differed between adults with asthma exacerbations and AECOPD. HRV-C was the HRV species most often observed in adult asthma exacerbations and AECOPD, although it did not worsen patients’ clinical outcomes relative to those of patients with other HRVs. Underlying disease-specific factors may be responsible for susceptibility to respiratory viruses.Trial registrationUMIN-CTR UMIN000031934.     

Eicosanoids seasonally impact pulmonary function in asthmatic patients with Japanese cedar pollinosis

BackgroundCondition of asthma in patients with asthma and concomitant seasonal allergic rhinitis (SAR) deteriorates during the Japanese cedar pollen (JCP) season. However, the underlying mechanisms remain unclear.MethodsWe analyzed seasonal variations in eicosanoid levels in the airways of patients with asthma and concomitant SAR sensitized to JCP (N = 29, BA-SAR-JCP group) and those not sensitized (N = 13, BA-AR-non-JCP group) during the JCP season. The association between changes in eicosanoid concentrations and pulmonary function was assessed. Exhaled breath condensate (EBC) was collected, and pulmonary function tests were performed during the JCP and non-JCP seasons. The cysteinyl leukotriene (CysLT), thromboxane B₂ (TXB₂), prostaglandin D₂-methoxime (PGD₂-MOX), and leukotriene B₄ (LTB₄) levels in the collected EBC were measured via enzyme-linked immunosorbent immunoassays.ResultsThe log CysLT levels significantly increased in the BA-SAR-JCP group during the JCP season compared with the non-JCP season (1.78 ± 0.55, 1.39 ± 0.63 pg/mL, mean ± standard deviation, respectively, p = 0.01) and those in the BA-AR-non-JCP group during the JCP season (1.39 ± 0.38 pg/mL, p = 0.04). Moreover, the log TXB₂ levels seemed to increase. However, the log LTB₄ and log PGD₂-MOX levels did not increase. The changes in the log CysLT levels during the two seasons were negatively correlated to forced expiratory volume in one second (FEV₁) in the BA-SAR-JCP group (r = −0.52, p < 0.01).ConclusionsIn the BA-SAR-JCP group, seasonal increases in eicosanoid levels in the airway likely promoted deterioration in pulmonary function despite optimal maintenance treatment.