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Background: Deteriorated sinusitis and increased adiposity relative to muscle mass may affect quality of life in patients with asthma. However, whether these effects are observed regardless of intrapulmonary pathology is unknown. Objectives: We evaluated the correlation of the cross-sectional ratio of abdominal visceral fat (VF) to erector spinae muscle (ESM) and sinus findings based on Lund-Mackey scoring system (LMS) on computed tomography (CT) with the impaired score of the Asthma Quality of Life Questionnaire (AQLQ), regardless of airway and parenchymal disease, in patients with asthma. Methods: We recruited participants from the Hokkaido-based severe asthma cohort who had completed AQLQ and CT examination at the entry. The participants were divided into high (highest) and low (other quartiles) groups on the bases of the extrapulmonary indices. Multivariate analysis examined the association of VF/ESM for the adiposity-to-muscle ratio and LMS with AQLQ after adjusting for the airway fractal dimension for airway index and percentage of low attenuation volume to lung volume for parenchymal index. Results: No significant differences were observed in VF/ESM and LMS in terms of sex. The AQLQ score in the high VF/ESM group and high LMS group was lower than those in low VF/ESM group and low LMS group (63 male and 100 female subjects). High VF/ESM (estimate [95% confidence interval] (-0.43 [-0.61, -0.25]) and high LMS scores (-0.22 [-0.41, -0.03]) were associated with low AQLQ scores when adjusted for age, body mass index, smoking status, blood eosinophil count, and intrapulmonary CT indices. Conclusions: Increased VF relative to ESM mass and high LMS may deteriorate asthma-related quality of life, regardless of presence of intrapulmonary disease.
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BACKGROUND AND OBJECTIVE: Mucus plugs and underlying airway tree structure can affect airflow limitation and prognosis in patients with chronic obstructive pulmonary disease (COPD), but their relative roles are unclear. This study used two COPD cohorts to examine whether mucus plugs on computed tomography (CT) were associated with airflow limitation and clinical outcomes independent of other airway structural changes and emphysema. METHODS: Based on visual CT assessment, patients with mucus plugs in 0, 1-2 and ≥3 lung segments were assigned to no-, low- and high-mucus groups. Loss of health-related independence and mortality were prospectively recorded for 3 and 10 years in the Kyoto-Himeji and Hokkaido cohorts, respectively. The percentages of the wall area of the central airways (WA%), total airway count (TAC) and emphysema were quantified on CT. RESULTS: Of 199 and 96 patients in the Kyoto-Himeji and Hokkaido cohorts, 34% and 30%, respectively, had high mucus scores. In both cohorts, TAC was lower in the high-mucus group than in the no-mucus group, whereas their emphysema severity did not differ. High mucus score and low TAC were independently associated with airflow limitation after adjustment for WA% and emphysema. In multivariable models adjusted for WA% and emphysema, TAC, rather than mucus score, was associated with a greater rate of loss of independence, whereas high mucus score, rather than TAC, was associated with increased mortality. CONCLUSION: Mucus plugs and lower airway branch count on CT had distinct roles in airflow limitation, health-related independence and mortality in patients with COPD.
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Background: Low respiratory function in young adulthood is one of the important factors in the trajectory leading to the future development of COPD, but its morphological characteristics are not well characterised. Methods: We retrospectively enrolled 172 subjects aged 40-49â years with ≥10 pack-years smoking history who underwent lung cancer screening by computed tomography (CT) and spirometry at two Japanese hospitals. Emphysema was visually assessed according to the Fleischner Society guidelines and classified into two types: centrilobular emphysema (CLE) and paraseptal emphysema (PSE). Airway dysanapsis was assessed with the airway/lung ratio (ALR), which was calculated by the geometric mean of the lumen diameters of the 14 branching segments divided by the cube root of total lung volume on a CT scan. Results: Among the subjects, CLE and PSE were observed in 20.9% and 30.8%, respectively. The mean ALR was 0.04 and did not differ between those with and without each type of emphysema. Multivariable regression analysis models adjusted for age, sex, body mass index and smoking status indicated that CLE and a low ALR were independently associated with lower forced expiratory volume in 1â s (FEV1)/forced vital capacity (estimate -1.64 (95% CI -2.68- -0.60) and 6.73 (95% CI 4.24-9.24), respectively) and FEV1 % pred (estimate -2.81 (95% CI -5.10- -0.52) and 10.9 (95% CI 5.36-16.4), respectively). Conclusions: CLE and airway dysanapsis on CT were independently associated with low respiratory function in younger smokers.
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BACKGROUND AND AIMS: Bronchial thermoplasty (BT) is a bronchoscopic treatment for adult patients with moderate to severe asthma. A systematic review was conducted to examine the efficacy of this treatment. METHODS: Randomized controlled comparing BT to a control in adult patients with moderate to severe asthma were added to the previously conducted systematic review. Literature published prior to July 2022 was selected. RESULTS: Four trials were included in this study. BT resulted in significant improvement in quality of life. However, no significant difference in asthma control was observed. Moreover, the incidence of severe adverse events during the treatment period was increased by BT. Furthermore, BT did not improve lung function, increase withdrawal from oral corticosteroids, reduce frequency of rescue medication usage, or increase the number of symptom-free days. CONCLUSION: From a risk-benefit perspective, there is insufficient evidence to support a recommendation of BT in adult patients with moderate to severe asthma.
Subject(s)
Asthma , Bronchial Thermoplasty , Adult , Humans , Quality of Life , Asthma/surgery , Asthma/drug therapy , Adrenal Cortex Hormones/therapeutic useABSTRACT
BACKGROUND: Associations of fractional exhaled nitric oxide (FeNO) with airway wall remodeling and mucus plugs remain to be explored in smokers and nonsmokers with asthma. Ultra-high-resolution computed tomography (U-HRCT), which allows accurate structural quantification of airways >1 mm in diameter, was used in this study to examine whether higher FeNO was associated with thicker walls of the 3rd to 6th generation airways and mucus plugging in patients with asthma. METHODS: The retrospective analyses included consecutive former smokers and nonsmokers with asthma who underwent U-HRCT in a hospital. The ratio of wall area to summed lumen and wall area was calculated as the wall area percent (WA%). Mucus plugging was visually scored. RESULTS: Ninety-seven patients with asthma (including 59 former smokers) were classified into low (<20 ppb), middle (20-35 ppb), and high (>35 ppb) FeNO groups (n = 24, 26, and 47). In analysis including all patients and subanalysis including nonsmokers or former smokers, WA% in the 6th generation airways was consistently higher in the high FeNO group than in the low FeNO group, whereas WA% in the 3rd to 5th generation airways was not. In multivariable models, WA% in the 6th generation airways and the rate of mucus plugging were higher in the high FeNO group than in the low FeNO group after adjusting for age, sex, body mass index, smoking status, lung volume, and allergic rhinitis presence. CONCLUSIONS: Higher FeNO may reflect the inflammation and remodeling of relatively peripheral airways in asthma in both former smokers and nonsmokers.
Subject(s)
Asthma , Mucus , Nitric Oxide , Smokers , Tomography, X-Ray Computed , Humans , Asthma/metabolism , Asthma/diagnostic imaging , Male , Female , Middle Aged , Nitric Oxide/metabolism , Mucus/metabolism , Adult , Retrospective Studies , Aged , Non-Smokers , Exhalation , Airway Remodeling , Smoking/adverse effects , Fractional Exhaled Nitric Oxide Testing , Breath Tests/methodsABSTRACT
INTRODUCTION: Notably, few studies have evaluated the recent changes in the prevalence of allergic diseases in young adults. Studies examining the risk of allergy in two populations with similar social backgrounds, other than the region in which they live, are rare. METHODS: First-year students from Hokkaido University were enrolled in this study between 2011 and 2019. A questionnaire survey was conducted to determine the annual prevalence of current wheeze, seasonal allergic rhinitis (SAR), and perennial allergic rhinitis (PAR) in nonsmoking young adults. Trends in the presence of these disease conditions were evaluated based on their hometowns (Hokkaido and outside Hokkaido separately) due to the low prevalence of cedar pollen allergies in Hokkaido. The association between these disease conditions and body mass index (BMI) was also assessed. RESULTS: The prevalence of current wheeze and PAR food allergies did not change in both regions. SAR showed a significantly increasing trend; however, the prevalence of SAR was higher among those whose place of origin was not Hokkaido. Current wheeze was positively associated with obesity (p < 0.05), whereas the high prevalence of SAR was not associated with body weight. In contrast, a lean body type was significantly associated with a higher prevalence of PAR (p < 0.05). DISCUSSION/CONCLUSION: The prevalence of current wheeze was stable and that of PAR has decreased over the past 9 years. However, the prevalence of SAR in Hokkaido has been increasing in Japanese young adults. A differential association between current wheeze and BMI was observed when comparing PAR and SAR.
Subject(s)
Hypersensitivity , Rhinitis, Allergic, Perennial , Rhinitis, Allergic, Seasonal , Humans , Young Adult , Prevalence , Hypersensitivity/epidemiology , Hypersensitivity/complications , Rhinitis, Allergic, Seasonal/epidemiology , Rhinitis, Allergic, Perennial/complications , Obesity/epidemiology , Obesity/complicationsABSTRACT
Recent advances in imaging analysis have enabled evaluation of ventilation and perfusion in specific regions by chest computed tomography (CT) and magnetic resonance imaging (MRI), in addition to modalities including dynamic chest radiography, scintigraphy, positron emission tomography (PET), ultrasound, and electrical impedance tomography (EIT). In this review, an overview of current functional imaging techniques is provided for each modality. Advances in chest CT have allowed for the analysis of local volume changes and small airway disease in addition to emphysema, using the Jacobian determinant and parametric response mapping with inspiratory and expiratory images. Airway analysis can reveal characteristics of airway lesions in chronic obstructive pulmonary disease (COPD) and bronchial asthma, and the contribution of dysanapsis to obstructive diseases. Chest CT is also employed to measure pulmonary blood vessels, interstitial lung abnormalities, and mediastinal and chest wall components including skeletal muscle and bone. Dynamic CT can visualize lung deformation in respective portions. Pulmonary MRI has been developed for the estimation of lung ventilation and perfusion, mainly using hyperpolarized 129Xe. Oxygen-enhanced and proton-based MRI, without a polarizer, has potential clinical applications. Dynamic chest radiography is gaining traction in Japan for ventilation and perfusion analysis. Single photon emission CT can be used to assess ventilation-perfusion (VË/QË) mismatch in pulmonary vascular diseases and COPD. PET/CT VË/QË imaging has also been demonstrated using "Galligas". Both ultrasound and EIT can detect pulmonary edema caused by acute respiratory distress syndrome. Familiarity with these functional imaging techniques will enable clinicians to utilize these systems in clinical practice.
Subject(s)
Pulmonary Disease, Chronic Obstructive , Pulmonary Emphysema , Humans , Positron Emission Tomography Computed Tomography , Lung/diagnostic imaging , Tomography, X-Ray Computed/methods , Magnetic Resonance Imaging/methodsABSTRACT
BACKGROUND: Real-time asthma exacerbation prediction and acute asthma attack detection are essential for patients with severe asthma. Peak expiratory flow (PEF) exhibits a potential for use in long-term asthma self-monitoring. However, the method for processing PEF calculations remains to be clarified. OBJECTIVE: To develop clinically applicable novel exacerbation predictors calculated using PEF records. METHODS: Previously proposed exacerbation predictors, including the slope of PEF, percentage predicted PEF, percentage best PEF, the highest PEF over the lowest PEF within specific periods, and PEF coefficient of variation, in addition to a novel indicator delta PEF moving average (ΔMA), defined as the difference between 14-day and 3-day average PEF values, along with moving average (MA) adjusted for PEF reference (%ΔMA), were verified using the Hokkaido-based Investigative Cohort Analysis for Refractory Asthma data of 127 patients with severe asthma from whom 73,503 PEF observations were obtained. Receiver operating characteristic curves for all predictors were drawn, and the corresponding areas under the curve (AUCs) were computed. Regression analysis for MA and percentage MA were conducted. RESULTS: The most outstanding performance was shown by ΔMA and %ΔMA, with AUC values of 0.659 and 0.665 in the univariate model, respectively. When multivariate models were incorporated with random intercepts for individual participants, the AUC for ΔMA and %ΔMA increased to 0.907 and 0.919, respectively. CONCLUSION: The MA and percentage MA are valuable indicators that should be considered when deriving predictors from the PEF trajectory for monitoring exacerbations in patients with severe asthma. TRIAL REGISTRATION: The Hokkaido-based Investigative Cohort Analysis for Refractory Asthma was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN ID: 000003254). https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000003917.
Subject(s)
Asthma , Humans , Asthma/diagnosis , Asthma/drug therapy , Peak Expiratory Flow RateABSTRACT
BACKGROUND: Effective use of lung volume data measured on computed tomography (CT) requires reference values for specific populations. This study examined whether an equation previously generated for multiple ethnic groups in the United States, including Asians predominantly composed of Chinese people, in the Multi-Ethnic Study of Atherosclerosis (MESA) could be used for Japanese people and, if necessary, to optimize this equation. Moreover, the equation was used to characterize patients with chronic obstructive pulmonary disease (COPD) and lung hyperexpansion. METHODS: This study included a lung cancer screening CT cohort of asymptomatic never smokers aged ≥40 years from two institutions (n = 364 and 419) to validate and optimize the MESA equation and a COPD cohort (n = 199) to test its applicability. RESULTS: In all asymptomatic never smokers, the variance explained by the predicted values (R2) based on the original MESA equation was 0.60. The original equation was optimized to minimize the root mean squared error (RMSE) by adjusting the scaling factor but not the age, sex, height, or body mass index terms of the equation. The RMSE changed from 714 ml in the original equation to 637 ml in the optimized equation. In the COPD cohort, lung hyperexpansion, defined based on the 95th percentile of the ratio of measured lung volume to predicted lung volume in never smokers (122 %), was observed in 60 (30 %) patients and was associated with centrilobular emphysema and air trapping on inspiratory/expiratory CT. CONCLUSIONS: The MESA equation was optimized for Japanese middle-aged and elderly adults.
Subject(s)
East Asian People , Lung Neoplasms , Pulmonary Disease, Chronic Obstructive , Pulmonary Emphysema , Aged , Humans , Middle Aged , Early Detection of Cancer , Forced Expiratory Volume , Japan , Lung/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Lung Volume Measurements , Pulmonary Disease, Chronic Obstructive/diagnostic imaging , Pulmonary Emphysema/diagnostic imaging , Tomography, X-Ray Computed/methods , Reference ValuesABSTRACT
BACKGROUND: Differences in the clinical impacts of fat mass index (FMI) and fat-free mass index (FFMI) remain unclear in patients with chronic obstructive pulmonary disease (COPD). We hypothesized that FMI and FFMI have different impacts on 1) emphysema and 2) pulmonary function and health-related quality of life of COPD patients. METHODS: Patients with COPD (n = 228), enrolled in a multicenter prospective 3-year cohort were classified into four groups based on baseline median FMI and FFMI values. Emphysema assessed as the ratio of low attenuation area to total lung volume (LAA%) on computed tomography, pulmonary function, and health-related quality of life assessed using the St. George's Respiratory Questionnaire (SGRQ) were compared. RESULTS: The four groups had statistically significant differences in LAA%, pulmonary function, and SGRQ scores. The Low FMI Low FFMI group exhibited the highest LAA%, lowest pulmonary function, and worst SGRQ scores among the four groups. In addition, these differences were consistent over 3 years. Multivariate analysis showed that low FMI was associated with high LAA%, low inspiratory capacity/total lung capacity (IC/TLC), and carbon monoxide transfer coefficient (KCO). In contrast, low FFMI was associated with these factors as well as worse SGRQ scores. CONCLUSION: FMI and FFMI have different effects on the clinical manifestations of COPD. Both low fat and muscle mass contributed to severe emphysema, whereas only low muscle mass contributed to worse health-related quality of life in patients with COPD.
Subject(s)
Emphysema , Pulmonary Disease, Chronic Obstructive , Pulmonary Emphysema , Humans , Prospective Studies , Quality of Life , Pulmonary Disease, Chronic Obstructive/diagnostic imaging , Lung/diagnostic imaging , Pulmonary Emphysema/diagnostic imaging , Body Mass Index , Body Composition/physiologyABSTRACT
Background: The mechanism of high transfer coefficients of the lungs for carbon monoxide (Kco) in non-smokers with asthma is explained by the redistribution of blood flow to the area with preserved ventilation, to match the ventilation perfusion. Objectives: To examine whether ventilation heterogeneity, assessed by pulmonary function tests, is associated with computed tomography (CT)-based vascular indices and Kco in patients with asthma. Methods: Participants were enrolled from the Hokkaido-based Investigative Cohort Analysis for Refractory Asthma (Hi-CARAT) study that included a prospective asthmatic cohort. Pulmonary function tests including Kco, using single breath methods; total lung capacity (TLC), using multiple breath methods; and CT, were performed on the same day. The ratio of the lung volume assessed using single breath methods (alveolar volume; VA) to that using multiple breath methods (TLC) was calculated as an index of ventilation heterogeneity. The volume of the pulmonary small vessels <5 mm2 in the whole lung (BV5 volume), and number of BV5 at a theoretical surface area of the lungs from the plural surface (BV5 number) were evaluated using chest CT images. Results: The low VA/TLC group (the lowest quartile) had significantly lower BV5 number, BV5 volume, higher BV5 volume/BV5 number, and higher Kco compared to the high VA/TLC group (the highest quartile) in 117 non-smokers, but not in 67 smokers. Multivariable analysis showed that low VA/TLC was associated with low BV5 number, after adjusting for age, sex, weight, lung volume on CT, and CT emphysema index in non-smokers (not in smokers). Conclusion: Ventilation heterogeneity may be associated with low BV5 number and high Kco in non-smokers (not in smokers). Future studies need to determine the dynamic regional system in ventilation, perfusion, and diffusion in asthma.
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BACKGROUND: The factors associated with longitudinal changes in diffusing capacity remain unclear among patients with COPD. Centrilobular emphysema (CLE) and paraseptal emphysema (PSE) are major emphysema subtypes that may have distinct clinical-physiological impacts in these patients. RESEARCH QUESTION: Are CLE and PSE differently associated with longitudinal changes in diffusing capacity and mortality in patients with COPD? STUDY DESIGN AND METHODS: This pooled analysis included 399 patients with COPD from two prospective observational COPD cohorts. CLE and PSE were visually assessed on CT scan according to the Fleischner Society statement. The diffusing capacity and transfer coefficient of the lung for carbon monoxide (Dlco and KCO) and FEV1 were evaluated at least annually over a 5-year period. Mortality was recorded over 10 years. Longitudinal changes in FEV1, Dlco, and KCO and mortality were compared between mild or less severe and moderate or more severe CLE and between present and absent PSE in each Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage. RESULTS: The Dlco and KCO decline was weakly associated with FEV1 and greater in GOLD stage 3 or higher than in GOLD stages 1 and 2. Furthermore, moderate or more severe CLE, but not present PSE, was associated with steeper declines in Dlco for GOLD stages 1 and 3 or higher and KCO for all GOLD stages independent of age, sex, height, and smoking history. The moderate or more severe CLE, but not present PSE, was associated with additional FEV1 decline and higher 10-year mortality among patients with GOLD stage 3 or higher. INTERPRETATION: A CT scan finding of moderate or more severe CLE, but not PSE, was associated with a subsequent accelerated impairment in diffusing capacity and higher long-term mortality in severe GOLD stage among patients with COPD.
Subject(s)
Emphysema , Pulmonary Disease, Chronic Obstructive , Pulmonary Emphysema , Humans , Lung/diagnostic imaging , Respiratory Function Tests , Pulmonary Diffusing Capacity , Forced Expiratory VolumeABSTRACT
BACKGROUND: Blood 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. METHODS: A 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. RESULTS: Among 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. CONCLUSIONS: We identified variations in the blood eosinophil counts and their contributing factors in patients with COPD and severe asthma.
Subject(s)
Asthma , Pulmonary Disease, Chronic Obstructive , Humans , Eosinophils , Cohort Studies , Asthma/diagnosis , Leukocyte CountABSTRACT
BACKGROUND: There are knowledge gaps in the potential role of Club cell 16-kDa secretory protein (CC16) in severe asthma phenotypes and type 2 inflammation, as well as the longitudinal effect of CC16 on pulmonary function tests and exacerbation risk in epidemiological studies. OBJECTIVE AND METHODS: To assess whether serum CC16 is associated with eosinophilic inflammation in patients with severe asthma. We also examined the effect of this protein on the annual decline in forced expiratory volume in the first second (FEV1) and the risk of exacerbation using a longitudinal approach. We recruited 127 patients with severe asthma from 30 hospitals/pulmonary clinics in Hokkaido, Japan. The least square means and standard error were calculated for T-helper 2 (Th2) biomarkers and pulmonary function test across CC16 tertiles at baseline. We did the same for asthma exacerbation and annual decline in FEV1 with 3 and 5 years' follow-up, respectively. RESULTS: We found that serum CC16 was inversely associated with sputum eosinophils and blood periostin in a dose-response manner. Baseline CC16 and FEV1/forced vital capacity ratio were positively associated in adjusted models (p for trend = 0.008). Patients with the lowest tertile of serum CC16 levels at baseline had a -14.3 mL decline in FEV1 than those with the highest tertile over 5 years of follow-up (p for trend = 0.031, fully adjusted model). We did not find any association of CC16 with exacerbation risk. CONCLUSION: Patients with severe asthma with lower circulatory CC16 had enhanced eosinophilic inflammation with rapid FEV1 decline over time.
Subject(s)
Asthma , Eosinophilia , Humans , Lung , Forced Expiratory Volume , Eosinophils , Eosinophilia/complications , InflammationABSTRACT
BACKGROUND: There is considerable heterogeneity among patients with emphysematous chronic obstructive pulmonary disease (COPD). We hypothesised that in addition to emphysema severity, ventilation distribution in emphysematous regions would be associated with clinical-physiological impairments in these patients. OBJECTIVE: To evaluate whether the discordance between respiratory volume change distributions (from expiration to inspiration) in emphysematous and non-emphysematous regions affects COPD outcomes using two cohorts. METHODS: Emphysema was quantified using a low attenuation volume percentage on inspiratory CT (iLAV%). Local respiratory volume changes were calculated using non-rigidly registered expiratory/inspiratory CT. The Ventilation Discordance Index (VDI) represented the log-transformed Wasserstein distance quantifying discordance between respiratory volume change distributions in emphysematous and non-emphysematous regions. RESULTS: Patients with COPD in the first cohort (n=221) were classified into minimal emphysema (iLAV% <10%; n=113) and established emphysema with high VDI and low VDI groups (n=46 and 62, respectively). Forced expiratory volume in 1 s (FEV1) was lower in the low VDI group than in the other groups, with no difference between the high VDI and minimal emphysema groups. Higher iLAV%, more severe airway disease and hyperventilated emphysematous regions in the upper-middle lobes were independently associated with lower VDI. The second cohort analyses (n=93) confirmed these findings and showed greater annual FEV1 decline and higher mortality in the low VDI group than in the high VDI group independent of iLAV% and airway disease on CT. CONCLUSION: Lower VDI is associated with severe airflow limitation and higher mortality independent of emphysema severity and airway morphological changes in patients with emphysematous COPD.
Subject(s)
Pulmonary Disease, Chronic Obstructive , Pulmonary Emphysema , Humans , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/diagnostic imaging , Pulmonary Emphysema/diagnostic imaging , Lung/diagnostic imaging , Lung Volume Measurements , Forced Expiratory Volume , Tomography, X-Ray Computed , Severity of Illness IndexABSTRACT
BACKGROUND: The physiological importance of mucus plugs in computed tomography (CT) imaging is being increasingly recognized. However, whether airway inflammation and smoking affect the association between mucus plugs and clinical-physiological outcomes in asthma remains to be elucidated. The objective of this study is to examine how airway inflammation and/or smoking affect the correlation of CT-based mucus plug scores with exacerbation frequency and airflow limitation indices in asthma. METHODS: A total of 168 patients with asthma who underwent chest CT and sputum evaluation were enrolled and classified in eosinophilic asthma (EA; n = 103) and non-eosinophilic asthma (NEA; n = 65) groups based on sputum eosinophil percentage (cut-off: 3%). The mucus plug score was defined as the number of lung segments with mucus plugs seen on CT. RESULTS: More mucus plugs were detected on CT scans in the EA group than in the NEA group, regardless of smoking status. Mucus plug score and exacerbation frequency during one year after enrollment were significantly associated in the EA group but not in the NEA group after adjusting for demographics, blood eosinophil count, and fractional exhaled nitric oxide. Mucus plug score was associated with percentage of predicted forced expiratory volume in 1 s in non-smoking individuals in the EA and NEA group and in smoking individuals in the EA group but not in the NEA group after adjusting for demographics. CONCLUSIONS: The association of mucus plug score with exacerbation frequency and reduced lung function may vary due to airway inflammatory profile and smoking status in asthma.
Subject(s)
Asthma , Smoking , Humans , Smoking/adverse effects , Eosinophils/physiology , Inflammation , Lung , Sputum , MucusABSTRACT
BACKGROUND: Two spirometry criteria have been proposed for early chronic obstructive pulmonary disease (COPD) in young smokers: 1) forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < the lower limit of normal (LLN), and 2) FEV1 decline ≥60 ml/year. These criteria have yet to be validated. This study explored clinical factors associated with these two spirometry criteria. METHODS: This retrospective study analysed medical check-up data from 13,010 consecutive subjects aged <50 years who underwent current and 3 previous spirometry tests in Japan. Current ≥10 pack-year smokers were the main focus of analysis; those meeting one or more spirometry criteria were diagnosed with early COPD. Early COPD was categorized into three subtypes: FEV1/FVC < LLN and FEV1 decline <60 ml/year (type 1), FEV1/FVC ≥ LLN and FEV1 decline ≥60 ml/year (type 2), and FEV1/FVC < LLN and FEV1 decline ≥60 ml/year (type 3). RESULTS: Of the 1579 current ≥ 10 pack-year smokers, 488 (30.9%) met the early COPD criteria. Multivariate multinomial logistic models adjusted for age, sex, height, body mass index (BMI) and smoking history indicated that past BMI increase and low exercise were associated with higher type 2 early COPD incidence (odds ratio (OR) [95% confidence interval (CI)] = 4.30 [3.10, 6.04], and 0.80 [0.69, 0.93], respectively) but not with higher type 1 incidence. A history of asthma was associated with higher type 3 incidence (OR [95% CI] = 1.98 [1.18, 3.07]). CONCLUSIONS: The 3 types of spirometry-based early COPD have different clinical factors. Their trajectories should be explored in longitudinal studies.
Subject(s)
Pulmonary Disease, Chronic Obstructive , Humans , Retrospective Studies , Spirometry , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Forced Expiratory Volume , Vital CapacityABSTRACT
At the time of writing of this manuscript, four biologics were clinically available for the treatment of severe asthma, and there were no established recommendations for the period of administration or timing of discontinuation of each biologic. We present a case of severe asthma that was well controlled with long-term omalizumab treatment; however, prolongation of the dosing intervals resulted in disease exacerbation that was refractory to omalizumab treatment despite the restoration of the recommended interval of administration. We suspect that the prolonged dosing intervals might have reduced the efficacy of omalizumab. We report this case because dosing intervals should be considered in clinical practice in cases of long-term omalizumab treatment.
Subject(s)
Anti-Asthmatic Agents , Asthma , Anti-Asthmatic Agents/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Asthma/drug therapy , Disease Progression , Humans , Omalizumab/therapeutic useABSTRACT
BACKGROUND: Quality of life (QoL) assessment is important in the management of severe asthma, and comorbidities and/or exacerbations may affect longitudinal QoL. However, there are few reports on the longitudinal assessment of QoL in patients with asthma over multiple years and its related factors. This study aimed to clarify the relationship of longitudinal changes in QoL with comorbidities and/or exacerbations during a prolonged observation period in patients with severe asthma. METHODS: A total of 105 subjects who participated in the Hokkaido-based Investigative Cohort Analysis for Refractory Asthma (Hi-CARAT) with a six-year follow-up were analyzed. QoL was assessed annually, using the Standardized Asthma Quality of Life Questionnaire, and the subjects were divided into three groups: (1) persistently good QoL, (2) persistently poor QoL, and (3) fluctuating QoL. Assessed comorbidities comprised depression, gastroesophageal reflux disease, and excessive daytime sleepiness (EDS), a key symptom of obstructive sleep apnea. RESULTS: Of 105 subjects with severe asthma, 53 (50%) were classified in the persistently good QoL group, 10 (10%) in the persistently poor QoL group, and 42 (40%) in the fluctuating QoL group. The persistently poor QoL group was associated with shorter time to hospitalization due to exacerbation and the presence of multiple comorbidities. In addition, the presence of EDS was an independent contributor to the fluctuating QoL group compared to the persistently good QoL group. CONCLUSIONS: The presence of multiple comorbidities and hospitalization due to exacerbation contribute to longitudinal changes in QoL in patients with severe asthma.
Subject(s)
Asthma , Gastroesophageal Reflux , Asthma/diagnosis , Asthma/epidemiology , Comorbidity , Hospitalization , Humans , Quality of LifeABSTRACT
INTRODUCTION: Club cell secretory protein-16 (CC16) is a major anti-inflammatory protein expressed in the airway; however, the potential role of CC16 on overweight/obese asthma has not been assessed. In this study, we examined whether obesity reduces airway/circulatory CC16 levels using experimental and epidemiological studies. Then, we explored the mediatory role of CC16 in the relationship of overweight/obesity with clinical asthma measures. METHODS: Circulating CC16 levels were assessed by ELISA in three independent human populations, including two groups of healthy and general populations and asthma patients. The percentage of cells expressing club markers in obese vs. non-obese mice and human airways was determined by immunohistochemistry. A causal mediation analysis was conducted to determine whether circulatory CC16 acted as a mediator between overweight/obesity and clinical asthma measures. RESULTS: BMI was significantly and monotonously associated with reduced circulating CC16 levels in all populations. The percentage of CC16-expressing cells was reduced in the small airways of both mice and humans with obesity. Finally, mediation analysis revealed significant contributions of circulatory CC16 in the association between BMI and clinical asthma measures; 21.8% of its total effect in BMI's association with airway hyperresponsiveness of healthy subjects (p = 0.09), 26.4% with asthma severity (p = 0.030), and 23% with the required dose of inhaled corticosteroid (p = 0.042). In logistic regression analysis, 1-SD decrease in serum CC16 levels of asthma patients was associated with 87% increased odds for high dose ICS requirement (p < 0.001). CONCLUSIONS: We demonstrate that airway/circulating CC16, which is inversely associated with BMI, may mediate development and severity in overweight/obese asthma.