Patients with asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) have been largely excluded from pivotal therapeutic trials and, as a result, its treatment remains poorly defined ...and lacking firm evidence. To date, there is no universally accepted definition of ACOS, which has made it difficult to understand its epidemiology or pathophysiology. Despite many uncertainties, there is emerging agreement that some of the key features of ACOS include persistent airflow limitation in symptomatic individuals 40 years of age and older, a well-documented history of asthma in childhood or early adulthood and a significant exposure history to cigarette or biomass smoke. In this perspective, we propose a case definition of ACOS that incorporates these key features in a parsimonious algorithm that may enable clinicians to better diagnose patients with ACOS and most importantly enable researchers to design therapeutic and clinical studies to elucidate its epidemiology and pathophysiology and to ascertain its optimal management strategies.
Asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) is characterized by persistent airflow limitation with several features usually associated with asthma and several features ...usually associated with COPD. ACOS may be a special phenotype of a spectrum of chronic obstructive airway diseases, in which asthma and COPD are at the two opposite ends. The prevalence of ACOS varies considerably due to differing criteria being applied for diagnosis. Patients with ACOS utilize a large proportion of medical resources. They are associated with more frequent adverse outcomes than those with asthma or COPD alone. ACOS is currently a diagnostic challenge for physicians because there are no specific biomarkers to differentiate ACOS from asthma or COPD. The approach to diagnosing ACOS depends on the population from which the patient originated. The management of ACOS should be individualized to ensure the most effective treatment with minimal side effects. In this paper, we review the diagnostic criteria of ACOS used in previous studies, propose practical approaches to diagnosing and managing ACOS and raise some research questions related to ACOS.
For case report illustrating this review, see Respirology Case Reports http://dx.doi.org/10.1002/rcr2.130
It is well known that correct use of inhalers plays a critical role in optimal inhalation therapy, but the impact of incorrect inhaler use on pulmonary drug delivery has not been quantitatively ...evaluated. The aim of this study was to investigate the frequency of holding inhalers at incorrect angles during the drug-loading step while using Turbuhaler® and to quantify the influence of the inhaler angle on in vitro pulmonary delivery. Thirty patients prescribed Turbuhaler® at Shiga University of Medical Science Hospital were enrolled. During inhalation, the participants’ inhalation techniques were assessed by clinical pharmacists. Additionally, the influence of the inhaler angle on pulmonary delivery of budesonide via Symbicort® Turbuhaler® was investigated using a Twin-Stage Liquid Impinger. Output efficiency (OE), stage 2 deposition (St2), and OE × St2 were calculated. An incorrect angle during the drug-loading step was observed in 33.3% of the participants. In vitro testing demonstrated that OE, an index of the loaded dose, significantly decreased by 73.3% at an incorrect angle, while St2, an index of the deagglomerating efficiency, was stable independent of the holding angle. OE × St2, indicating the bronchial and pulmonary drug delivery amount, decreased by 76.9%. An incorrect holding angle reduced the loaded dose, resulting in decreased pulmonary delivery. Error in the inhaler angle occurs frequently and demonstrates a considerable impact on pulmonary drug delivery. Hence, it is necessary to assess the Turbuhaler® angle during inhalation.
Emphysematous change as assessed by CT imaging has been reported to correlate with COPD prognostic factors such as FEV1 and diffusing capacity of the lung for carbon monoxide (Dlco). However, few ...studies have assessed the relationship between CT scan assessment and COPD mortality from mild to severe stages of the disease. In this study, we analyzed this relationship in patients with various stages of COPD.
Two hundred and fifty-one outpatients with stable COPD were included in the study. CT scan and pulmonary function tests were performed at study entry in a single institution. The percentage of low attenuation area was measured to quantitatively evaluate emphysematous change with a custom-made software. Prognostic data also were collected, and the median follow-up time was 8 years.
Of the 251 patients, 79 died, with 40 classified as respiratory deaths not involving lung cancer. Univariate Cox analysis revealed that emphysematous change as assessed by CT scan, lung function, age, or BMI were significantly correlated with mortality. Multivariate analysis revealed that emphysematous change as assessed by CT scan had the best association with mortality.
Emphysematous change as assessed by CT scan predicts respiratory mortality in outpatients with various stages of COPD.
Immune-mediated pneumonitis has a high mortality rate; however, information regarding the related risk factors remains limited. This study aimed to analyze risk factors for pneumonitis, including ...smoking and lung metastasis (LM), in patients with extrapulmonary primary tumors.
Data of 110 patients treated with immune checkpoint inhibitors (ICIs) (nivolumab/pembrolizumab) for treating extrapulmonary primary tumors at the Shiga University of Medical Science Hospital between January 2015 and December 2019 were retrospectively collected. The association between the onset of pneumonitis and treatment-related factors was analyzed by logistic regression. The severity of pneumonitis was graded according to the Common Terminology Criteria for Adverse Events version 5.0. Risk factors, such as the absence or presence of interstitial lung disease (ILD) and LM, or other clinical factors, including smoking status before ICI administration, were analyzed.
Multivariate analyses indicated that the amount of smoking was significantly associated with an increase in the development of all-grade pneumonitis types (odds ratio (OR) = 20.33, 95% confidence interval (CI) = 20.03-20.66; p = 0.029). LM and ILD were significantly related to an increase in the development of symptomatic pneumonitis (≥ Grade 2) (OR = 10.08, 95% CI = 1.69-199.81; p = 0.076, and OR = 6.76, 95% CI = 1.13-40.63; p = 0.037, respectively).
Pre-screening for ILD and LM and recognizing patients' smoking history is important for determining the risk of ICI-induced pneumonitis and allowing safe ICI administration.
Aim: We aimed to investigate the association between reduced lung function and cerebral small vessel diseases via cranial magnetic resonance imaging (MRI) in the cross-sectional study of the general ...Japanese population.Methods: We recruited participants aged ≥40 years from the general population of a single city in Japan. We clarified the comorbidities and treatments, smoking habits, second-hand smoke exposure, current alcohol consumption, education level, exercise habits, and occupation. The pulmonary function test was performed to assess the forced expiratory volume in 1 second (FEV1) % predicted and forced vital capacity (FVC) % predicted values. Cranial MRI was performed to evaluate the white matter lesions (WMLs) and lacunar infarcts. We examined the association of the WMLs and lacunar infarcts with a 1-standard deviation (SD) lower in the FEV1 % predicted and FVC % predicted, on the basis of the smoking status.Results: A total of 473 men were examined. The association of WMLs and lacunar infarcts with the spirometry-based indices were significant only in never smokers. The association between lung function impairment and cerebral small vessel disease did not change after further adjusting for second-hand smoke exposure.Conclusion: In a community-based sample of Japanese men, we found an association between reduced lung function and WMLs and lacunar infarcts in never smokers.
Honeycombing on high-resolution computed tomography (HRCT) images is a key finding in idiopathic pulmonary fibrosis (IPF). In IPF, honeycombing area determined by quantitative CT analysis is ...correlated with pulmonary function test findings. We hypothesized that quantitative CT-derived honeycombing area (HA) might predict mortality in patients with IPF.
Chest HRCT images of 52 IPF patients with definite usual interstitial pneumonia (UIP) pattern were retrospectively evaluated. Mortality data up to July 31, 2016, were recorded. Using a computer-aided system, HA and percentage of HA (%HA) were measured quantitatively. Predictors of 3-year mortality were evaluated using logistic regression models.
The median %HA, %predicted forced vital capacity (FVC) and composite physiologic index (CPI) were 3.8%, 83.6%, and 33.6, respectively. According to GAP (gender, age, and physiology) stage, 20, 14, and 5 patients were classified under stages I-II-III, respectively. Percentage of HA was significantly correlated with %FVC, CPI, and GAP stage (all, p < 0.001). In univariate analysis, %HA, %FVC, and CPI were statistically significant predictors of mortality. In multivariate analysis using the stepwise regression method, only %HA (odds ratio OR, 1.27; p = 0.011) was a significant independent predictors of mortality. Patients with %HA ≥ 4.8% had significantly lower survival rates than those with lesser %HA (median survival time, 1.3 vs 5.0 years; log-rank test; p < 0.001).
Quantitative CT-derived HA might be an important and independent predictor of mortality in IPF patients with definite UIP pattern.
Background Periostin, an extracellular matrix protein, contributes to subepithelial thickening in asthmatic airways, and its serum levels reflect airway eosinophilic inflammation. However, the ...relationship between periostin and the development of airflow limitation, a functional consequence of airway remodeling, remains unknown. Objective We aimed to determine the relationship between serum periostin levels and pulmonary function decline in asthmatic patients on inhaled corticosteroid (ICS) treatment. Methods Two hundred twenty-four asthmatic patients (average age, 62.3 years) treated with ICS for at least 4 years were enrolled. Annual changes in FEV1 , from at least 1 year after the initiation of ICS treatment to the time of enrollment or later (average, 16.2 measurements over 8 years per individual), were assessed. At enrollment, clinical indices, biomarkers that included serum periostin, and periostin gene polymorphisms were examined. Associations between clinical indices or biomarkers and a decline in FEV1 of 30 mL or greater per year were analyzed. Results High serum periostin levels (≥95 ng/mL) at enrollment, the highest treatment step, higher ICS daily doses, a history of admission due to asthma exacerbation, comorbid or a history of sinusitis, and ex-smoking were associated with a decline in FEV1 of 30 mL or greater per year. Multivariate analysis showed that high serum periostin, the highest treatment step, and ex-smoking were independent risk factors for the decline. Polymorphisms of periostin gene were related to higher serum periostin levels (rs3829365) and a decline in FEV1 of 30 mL or greater per year (rs9603226). Conclusions Serum periostin appears to be a useful biomarker for the development of airflow limitation in asthmatic patients on ICS.
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