Sustained remission induced by 2 years of treatment with benralizumab in patients with severe eosinophilic asthma and nasal polyposis.

BACKGROUND AND OBJECTIVE: Several randomized controlled trials (RCTs) have shown that benralizumab is characterized by a good profile of efficacy and safety, thereby being potentially able to elicit clinical remission on-treatment of severe eosinophilic asthma (SEA). The main goal of this multicentre observational study was to verify the effectiveness of benralizumab in inducing a sustained remission on-treatment of SEA in patients with or without comorbid chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Throughout 2 years of treatment with benralizumab, a four-component evaluation of sustained remission of SEA was performed, including the assessment of SEA exacerbations, use of oral corticosteroids (OCSs), symptom control and lung function. RESULTS: The present study recruited 164 patients suffering from SEA. After 24 months of add-on biological therapy with benralizumab, 69 (42.1%) achieved the important target of sustained remission on-treatment (exacerbation rate = 0, OCS dose = 0, pre-bronchodilator FEV1 ≥80% pred., ACT score ≥ 20). During the same period, a persistent improvement of CRSwNP (SNOT-22 < 30, NP recurrence = 0) was observed in 33 (40.2%) out of 82 subjects with concomitant NP. The latter comorbidity and post-bronchodilator reversibility of airflow limitation were two independent predictors of sustained remission on-treatment (OR = 2.32, p < 0.05 and OR = 5.59, p < 0.01, respectively). CONCLUSION: Taken together, the results of this real-life clinical investigation indicate that benralizumab can induce a sustained remission on-treatment of SEA, especially in those patients with comorbid CRSwNP and reversible airflow limitation.

Phenotype to Treatable Traits-Based Management in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD), a heterogeneous respiratory disease driven by various genetic and environmental factors, presents significant challenges in diagnosis and management. Traditional approaches focused on phenotypic classification, but recent paradigms emphasize identifying and addressing treatable traits to personalize treatment strategies. Treatable traits facilitate personalized interventions, optimizing symptom control, and reducing exacerbation risk. Dyspnea and exacerbations, recognized as key traits, guide treatment decisions and follow-up management. Various interventions, including bronchodilators, corticosteroids, and lifestyle modifications, target specific traits like airway inflammation, mucus overproduction, and emphysema. Strategies for assessing and addressing treatable traits during initial encounters and follow-up visits enhance disease monitoring and treatment efficacy. Comprehensive trait assessment demands resources and specialized monitoring, posing barriers to widespread implementation. The lack of standardized protocols and evolving evidence further complicates decision-making and clinical practice. Despite these challenges, the shift toward treatable traits-based management signifies a pivotal advancement in COPD care, emphasizing holistic approaches tailored to individual patient needs. Recognizing and addressing treatable traits offers personalized interventions, enhancing symptom control and disease management. Embracing treatable traits-based approaches holds promise for improving clinical outcomes and enhancing the quality of life for individuals living with COPD.

Expiratory and inspiratory resistance and reactance from respiratory oscillometry defining expiratory flow limitation in obstructive lung diseases.

BACKGROUND: Expiratory flow limitation (EFL) during tidal breathing and lung hyperinflation have been identified as major decisive factors for disease status, prognosis and response to therapy in obstructive lung diseases. AIM: To investigate the delta values between expiratory and inspiratory resistance and reactance, measured using respiratory oscillometry and its correlation with air trapping and symptoms in subjects with obstructive lung diseases. METHODS: Four hundred and seventy-one subjects (96 with chronic obstructive pulmonary disease [COPD], 311 with asthma, 30 healthy smokers and 34 healthy subjects) were included. Spirometry, body plethysmography and respiratory oscillometry measurements were performed and the differences between the expiratory and inspiratory respiratory oscillometry values (as delta values) were calculated. Questionnaires regarding symptoms and quality of life were administered. RESULTS: Patients with COPD and healthy smokers had an increased delta resistance at 5 Hz (R5) compared with patients with asthma (p < 0.0001 and p = 0.037, respectively) and healthy subjects (p = 0.0004 and p = 0.012, respectively). Patients with COPD also had higher values of ΔR5-R19 than healthy subjects (p = 0.0001) and patients with asthma (p < 0.0001). Delta reactance at 5 Hz (X5) was significantly more impaired in COPD patients than in asthma and healthy subjects (p < 0.0001 for all). There was a correlation between the ratio of residual volume and total lung capacity and ΔR5 (p = 0.0047; r = 0.32), ΔR5-R19 (p = 0.0002; r = 0.41) and ΔX5 (p < 0.0001; r = -0.44), for all subjects. ΔX5 correlated with symptoms in COPD, healthy smokers and patients with asthma. In addition, ΔR5 correlated with asthma symptoms. CONCLUSION: EFL was most prominent in parameters measuring peripheral resistance and reactance and correlated with air trapping and airway symptoms.

Safety and efficacy of bronchial thermoplasty in refractory asthma with severe obstructive respiratory dysfunction.

BACKGROUND: Bronchial thermoplasty (BT) is a recently developed non-pharmacological therapy for refractory bronchial asthma. Although increasing evidence has suggested that BT is effective for various phenotypes of severe asthma, its safety and efficacy in patients with severe irreversible impaired lung function are unclear. OBJECTIVES: To assess the efficacy and safety of BT in patients with refractory asthma, including patients with a severely impaired forced expiratory volume in 1 second (FEV1). DESIGN: This was a single-center, retrospective, observational cohort study. METHODS: We retrospectively reviewed the medical records of 15 patients with refractory asthma (Global Initiative for Asthma step 4 or 5), including patients with severely impaired airflow limitation (% predicted pre-bronchodilator FEV1 <60%), who had undergone BT between June 2016 and January 2022. We analyzed the efficacy (change in asthma symptoms, exacerbation rate, pulmonary function, asthma medication, and serum inflammatory chemokine/cytokines before and after BT) and complications in all patients. We compared these data between patients with severe obstructive lung dysfunction [group 1(G1)] and patients with FEV1 ⩾ 60% [group 2 (G2)]. RESULTS: Six patients were in G1 and nine were in G2. Clinical characteristics, T2 inflammation, and concurrent treatment were equivalent in both groups. BT significantly improved asthma-related symptoms (measured using the Asthma Control Test and Asthma Quality of Life Questionnaire scores) in both groups. FEV1 was significantly improved in G1 but not in G2. Four patients in G2, but none in G1, experienced asthma exacerbation requiring additional systemic corticosteroids (including two requiring prolonged hospitalization) after BT. Long-term responders (patients who reduced systemic or inhaled corticosteroid without newly adding biologics in a follow-up > 2 years) of BT were identified in G1 and G2 (n = 2, 33.3% and n = 4, 44.4%, respectively). CONCLUSION: BT in patients with refractory asthma and severe airflow limitation is equally safe and efficacious as that in patients with moderate airflow limitation.

Coffee consumption was associated with a lower prevalence of airflow limitation in postmenopausal women.

BACKGROUND: Several studies have suggested a potential correlation between menopause and airflow limitation. However, the presence of protective factors in postmenopausal women remains uncertain. Therefore, our study seeks to examine potential protective factors associated with a reduced prevalence of airflow limitation among postmenopausal women. METHODS: Postmenopausal women were recruited from the Taiwan Biobank for this cross-sectional study. Airflow limitation was defined by a forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) ratio <0.7. The participants were categorized into two groups: non-coffee drinkers and coffee drinkers, and the association between coffee consumption and airflow limitation was examined using binary logistic regression models. RESULTS: A total of 8149 women with available information were enrolled. Compared to the non-coffee drinkers, the coffee drinkers had a significantly lower prevalence of airflow limitation (7% vs. 5%). The odds ratio (OR) for airflow limitation was lower in the coffee drinkers than in the non-coffee drinkers (OR = 0.77; 95% confidence interval [CI] = 0.63 to 0.94) after adjusting for confounding factors. We also examined the association between daily coffee consumption in cups and airflow limitation. The women who consumed ≥2 cups of coffee per day had an OR of 0.74 (95% CI = 0.59 to 0.94) compared to those who did not consume coffee. CONCLUSIONS: Our results suggest that habitual coffee consumption is associated with a reduction in the prevalence of airflow limitation in postmenopausal women, warranting further prospective studies to explore possible causal effects and mechanisms.

Severity of Airflow Obstruction Based on FEV1/FVC vs FEV1% of Predicted in the General US Population.

RATIONALE: According to GOLD, the ratio of FEV1/FVC is used to confirm airflow obstruction in COPD diagnosis, whereas FEV1% of predicted (FEV1%pred) is used for severity grading. STaging of Airflow obstruction by the FEV1/FVC Ratio (STAR) and its prediction of adverse outcomes has not been evaluated in general populations. OBJECTIVE: To compare the STAR (FEV1/FVC) versus GOLD (FEV1%pred) classification for the severity of airflow limitation in terms of exertional breathlessness and mortality in the general US population. METHODS: Severity stages according to STAR and GOLD were applied to the multi-ethnic National Health and Nutrition Examination Survey (NHANES) 2007-2012 survey including ages 18-80 years, using post-bronchodilatory FEV1/FVC<0.70 to define airflow obstruction in both staging systems. Prevalence of severity stages STAR 1-4 and GOLD 1-4 was calculated and associations with breathlessness and mortality were analyzed by multinomial logistic regression and Cox regression, respectively. RESULTS: STAR versus GOLD severity staging of airflow obstruction showed similar associations with breathlessness and all-cause mortality, regardless of ethnicity/race. In those with airflow obstruction, the correlation between the two classification systems was 0.461 (p<0.001). STAR reclassified 59% of GOLD stage 2 as having mild airflow obstruction (STAR 1). STAR 1 was more clearly differentiated from the non-obstructive compared to GOLD stage 1 in terms of both breathlessness and mortality. CONCLUSIONS: FEV1/FVC and FEV1%pred as measures of severity of airflow limitation show similar prediction of breathlessness and mortality in the adult US population across ethnicity groups. However, stage 1 differed more clearly from non-obstructive based on FEV1/FVC than FEV1%pred. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Relief of Airflow Limitation and Airway Inflammation by Endoscopic Sinus Surgery in a Patient with Severe Asthma with Eosinophilic Chronic Rhinosinusitis.

Although endoscopic sinus surgery (ESS) is beneficial in improving asthma symptoms, its impact on the lung function in patients with asthma and chronic rhinosinusitis remains unclear. We herein report a case of severe asthma with eosinophilic chronic rhinosinusitis, in which ESS substantially improved airflow limitation and concomitantly reduced fractional exhaled nitric oxide and blood eosinophil counts. ESS likely relieved airflow limitation by suppressing type 2 inflammatory pathways. This case highlights ESS as a promising strategy for achieving clinical remission in patients with severe asthma and chronic rhinosinusitis.

Circulating biomarkers of airflow limitation across the life span.

BACKGROUND: Airflow limitation is a hallmark of chronic obstructive pulmonary disease, which can develop through different lung function trajectories across the life span. There is a need for longitudinal studies aimed at identifying circulating biomarkers of airflow limitation across different stages of life. OBJECTIVES: This study sought to identify a signature of serum proteins associated with airflow limitation and evaluate their relation to lung function longitudinally in adults and children. METHODS: This study used data from 3 adult cohorts (TESAOD [Tucson Epidemiological Study of Airway Obstructive Disease], SAPALDIA [Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults], LSC [Lovelace Smoker Cohort]) and 1 birth cohort (TCRS [Tucson Children's Respiratory Study]) (N = 1940). In TESAOD, among 46 circulating proteins, we identified those associated with FEV1/forced vital capacity (FVC) percent (%) predicted levels and generated a score based on the sum of their z-scores. Cross-sectional analyses were used to test the score for association with concomitant lung function. Longitudinal analyses were used to test the score for association with subsequent lung function growth in childhood and decline in adult life. RESULTS: After false discovery rate adjustment, serum levels of 5 proteins (HP, carcinoembryonic antigen, ICAM1, CRP, TIMP1) were associated with percent predicted levels of FEV1/FVC and FEV1 in TESAOD. In cross-sectional multivariate analyses the 5-biomarker score was associated with FEV1 % predicted in all adult cohorts (meta-analyzed FEV1 decrease for 1-SD score increase: -2.9%; 95% CI: -3.9%, -1.9%; P = 2.4 × 10-16). In multivariate longitudinal analyses, the biomarker score at 6 years of age was inversely associated with FEV1 and FEV1/FVC levels attained by young adult life (P = .02 and .005, respectively). In adults, persistently high levels of the biomarker score were associated with subsequent accelerated decline of FEV1 and FEV1/FVC (P = .01 and .001). CONCLUSIONS: A signature of 5 circulating biomarkers of airflow limitation was associated with both impaired lung function growth in childhood and accelerated lung function decline in adult life, indicating that these proteins may be involved in multiple lung function trajectories leading to chronic obstructive pulmonary disease.

Association between periodontal diseases and chronic obstructive pulmonary disease: Evidence from sequential cross-sectional and prospective cohort studies based on UK Biobank.

AIM: To investigate the association between periodontal diseases, airflow limitation and incident chronic obstructive pulmonary disease (COPD) in a large-scale prospective UK Biobank cohort. MATERIALS AND METHODS: Our approach comprised a cross-sectional study and a prospective cohort. Periodontal diseases were determined based on the participants' self-reported dental symptoms, including painful gums, bleeding gums and loose teeth. Logistic regression and Cox proportional hazards models were used to evaluate the association of periodontal diseases with airflow limitation and incident COPD in the cross-sectional study and the prospective cohort, respectively. RESULTS: The cross-sectional study involved 495,610 participants. Multivariable analysis found that periodontal diseases were significantly associated with airflow limitation (odds ratio = 1.036, 95% confidence interval [CI]: 1.015-1.059). The cohort study included 379,266 participants with a median follow-up period of 12.68 years. An elevated risk of incident COPD was associated with the presence of periodontal diseases (hazard ratio: 1.248, 95% CI: 1.174-1.326). The effect was consistent among subgroups, including baseline age (≤65 or >65 years), sex, smoking status and diabetes mellitus. CONCLUSIONS: Periodontal diseases are associated with airflow limitation and elevated COPD incidence. Maintaining good periodontal health in patients with chronic bronchitis and emphysema may help prevent the onset of COPD.

Incidence of bacterial respiratory infection and pneumonia in people with HIV with and without airflow limitation.

OBJECTIVES: We aimed to determine the incidence rate, pathogen composition, and risk factors, particularly airflow limitation, associated with bacterial respiratory infection and pneumonia in a prospective cohort of well-treated people with HIV (PWH) between 2015-2021. METHODS: We included 1007 PWH from the Copenhagen Comorbidity in HIV infection (COCOMO) study. Spirometry was performed at inclusion. Microbiology samples were collected prospectively. Cumulative incidence was determined by the Aalen-Johansen estimator. Cox proportional hazard models were used to calculate risk factors, adjusted for traditional and HIV-specific variables. RESULTS: The incidence rates of first bacterial respiratory infection and pneumonia were 12.4 (95% CI 9.7-15.5) and 5.5 (95% CI: 3.8-7.7) per 1000 person-years, respectively. The cumulative incidence of pneumonia was four times higher in PWH with airflow limitation (11.8% vs 3.2%, P <0.001). Risk factors for bacterial respiratory infection were airflow limitation (hazard ratio [HR] 2.9, [95% CI: 1.7-5.1], P <0.001), smoking (HR 2.3, [95% CI: 1.4-3.8], P <0.001), and previous AIDS-defining event (HR 2.0, [95% CI: 1.2-3.3], P = 0.009). For pneumonia, airflow limitation (HR 2.7, [95% CI: 1.2-6.3], P = 0.016), smoking (HR 2.5, [95% CI: 1.2-5.4], P = 0.016), and older age (HR 1.5, [95% CI: 1.1-2.1], P = 0.015) were identified as risk factors. CONCLUSIONS: Increased emphasis on airflow limitation prevention, including smoking cessation, may reduce the burden of bacterial respiratory infection and pneumonia in PWH.

Short-Term Benefits of Smoking Cessation Improve Respiratory Function and Metabolism in Smokers.

Background: Cigarette smoke exposure is the main preventable cause of chronic obstructive pulmonary disease (COPD). Airflow limitation is closely associated with smoking exposure. Smoking could also interfere with lipid metabolism. Aim: To determine the respiratory functional and metabolic changes after smoking cessation in smokers in the short term. Methods: All patients were current smokers. They were assessed by spirometry and questionnaires such as COPD assessment test(CAT), modified Medical Research Council (mMRC) test for dyspnea, Fagestrom's test for nicotine dependence. Exhaled CO was detected in order to evaluate smoking exposure and smoking cessation (normal value<7 ppm). A blood sampling was eventually taken for vitamin D and cholesterol assay. All patients underwent therapy with counselling and varenicline as first-line treatment according to its schedule. Detection time: at baseline and one month after smoking cessation. Results: All patients quit smoking during treatment. The mean age was 62 with a prevalence of males. The analysis revealed the following mean values at baseline: CAT mean score was 15, pack-years 35.5, Fagestrom's Test mean score 5.0. The West's value was 8.5, whereas Body mass index (BMI) was 25.5.Cigarette daily consumption mean value was 22.5. The comparison before and at follow up one month after smoking cessation about functional and metabolic parameters, show us the following results: FEV 1 was increased by 200 mL (p<0.02), FEF 25/75 was improved as well as mMRC test. The eCO was dropped to as low as 8 ppM. Interestingly the vitamin D level was increased from 25 to 28 ng/mL without any support therapy. The cholesterol total level was reduced and CAT value and DLCO were also significantly improved. Conclusion: Quit smoking is useful to improve symptoms, respiratory function and metabolic parameters in the short term.

Respiratory Symptoms, Disease Burden, and Quality of Life in Australian Adults According to GOLD Spirometry Grades: Data from the BOLD Australia Study.

Purpose: Population data on the burden of chronic obstructive pulmonary disease (COPD) are often based on patient-reported diagnoses of COPD, emphysema or chronic bronchitis, without spirometry. We aimed to investigate the relationship between health burden, quality of life and severity of airway obstruction in Australian adults aged ≥40 years. Methods: We used data from the BOLD Australia study, which included randomly selected adults aged ≥40 years from six study sites to reflect the sociodemographic and geographic diversity of the Australian population (n = 3522). Participants with post-bronchodilator airflow limitation (ratio of forced expiratory volume in 1 second FEV1 to forced vital capacity <0.7) were grouped by GOLD spirometry grades 1-4. Quality of life was assessed with Short Form 12 (SF-12) Health Survey Questionnaire. Health burden was assessed as lost time off work or social activities, and healthcare utilization. Results: Of the study sample, 2969 participants did not have airflow limitation, 294 (8.4%) were classified as GOLD Grade 1, 212 (6.0%) as GOLD 2 and 43 (1.2%) as GOLD 3-4. Participants with higher GOLD grades had more respiratory symptoms, more comorbidities and greater burden than those with lower GOLD grades. The scores of mental and physical subscales of SF-12 were lower, indicating worse quality of life, from the no airflow limitation group to the GOLD 3-4 group (P = 0.03 and P < 0.001, respectively). Conclusion: Greater airflow limitation is associated with greater burden and poor quality of life. Interventions to prevent, or reduce the level of, airflow limitation will reduce the symptom burden and improve quality of life for patients.

Repurposing catheter ablation work-up to detect expiratory airflow limitation in patients with atrial fibrillation.

Background: In atrial fibrillation (AF) patients, presence of expiratory airflow limitation may negatively impact treatment outcomes. AF patients are not routinely screened for expiratory airflow limitation, but existing examinations can help identify at-risk individuals. We aimed to assess the diagnostic value of repurposing existing assessments from the pre-ablation work-up to identify and understand the characteristics of affected patients. Methods: We screened 110 consecutive AF patients scheduled for catheter ablation with handheld spirometry. Routine pre-ablation work-up included cardiac computed tomographic angiography (CCTA), transthoracic echocardiography and polygraphy. CCTA was analyzed qualitatively for emphysema and airway abnormalities. Multivariate logistic regression analysis was performed to determine predictors of expiratory airflow limitation. Results: We found that 25 % of patients had expiratory airflow limitation, which was undiagnosed in 86 % of these patients. These patients were more likely to have pulmonary abnormalities on CCTA, including emphysema (odds ratio [OR] 4.2, 95 % confidence interval [CI] 1.12-15.1, p < 0.05) and bronchial wall thickening (OR 2.6, 95 % CI 1.0-6.5, p < 0.05). The absence of pulmonary abnormalities on CCTA accurately distinguished patients with normal lung function from those with airflow limitation (negative predictive value: 85 %). Echocardiography and polygraphy did not contribute significantly to identifying airflow limitation. Conclusions: In conclusion, routine pre-ablation CCTA can detect pulmonary abnormalities in AF patients with airflow limitation, guiding further pulmonary assessment. Future studies should investigate its impact on ablation procedure success.

Serum-Creatinine-to-Cystatin C-to-Waist-Circumference Ratios as an Indicator of Severe Airflow Limitation in Older Adults.

BACKGROUND: This study aimed to investigate the association between the serum-creatinine-to-cystatin C-to-waist-circumference (CCR/WC) ratio with lung function and severe airflow limitation (SAL). METHODS: The data were derived from the China Health and Retirement Longitudinal Study. Peak expiratory flow (PEF) was used as a measure of lung function parameter. Logistic and linear regression were utilized separately to evaluate the relationship between the CCR/WC ratio with PEF and SAL in baseline. Restricted cubic spline was used to explore potential non-linear associations between the CCR/WC ratio and SAL. Cox proportional-hazards models were used to assess the association between CCR/WC quartiles and the risk of new-onset SAL. RESULTS: A total of 6105 participants were included. This study revealed a positive association between the CCR/WC ratio and lung function (PEF: ß [partial coefficient]: 25.95, 95%CI: 12.72 to 39.18, p < 0.001; PEF/PEF prediction: ß = 0.08, 95%CI: 0.05 to 0.12, p < 0.001) and an inverse association relationship with SAL (OR [odds ratio]: 0.64, 95% confidence interval [CI]: 0.47 to 0.85, p = 0.003). Subgroup analysis showed a significant association between the CCR/WC ratio and SAL in males (OR: 0.58, 95% CI: 0.37 to 0.90, p = 0.017) but not in females (p = 0.059). Cox regression analysis revealed a decreased risk of SAL in the quartiles (Q2-4) compared to the first quartile of the CCR/WC ratio (hazard ratios [HRs]: 0.49 to 0.73, all p < 0.05). CONCLUSIONS: This study highlights a positive association between the CCR/WC ratio and lung function, with a potential protective effect against SAL.

Impact of the metabolic syndrome on cardiopulmonary morbidity and mortality in individuals with lung function impairment: a prospective cohort study of the Danish general population.

Background: Whether the metabolic syndrome plays a role for the prognosis of individuals with lung function impairment (preserved ratio impaired spirometry (PRISm) or airflow limitation) is unclear. We hypothesised that the metabolic syndrome in individuals with lung function impairment is associated with increased cardiopulmonary morbidity and mortality. Methods: The Copenhagen General Population Study was initiated in 2003 based on a random sample of white men and women aged 20-100 years drawn from the Danish general population. The risk of ischemic heart disease/heart failure, respiratory disease, and all-cause mortality was analysed with Cox models adjusted for age, sex, current smoking, and asthma during 15 years of follow-up. Findings: Among 106,845 adults, 86,159 had normal lung function, 6126 had PRISm, and 14,560 had airflow limitation. We observed 10,448 hospital admissions for ischemic heart disease/heart failure, 21,140 for respiratory disease, and 11,125 deaths. Individuals with versus individuals without the metabolic syndrome generally had higher 5-year absolute risk of all outcomes, including within those with normal lung function, mild-moderate-severe PRISm, and very mild-mild-moderate-severe airflow limitation alike. Compared to individuals without the metabolic syndrome and with normal lung function, those with both the metabolic syndrome and severe PRISm had hazard ratios of 3.74 (95% CI: 2.53-5.55; p < 0.0001) for ischemic heart disease/heart failure, 5.02 (3.85-6.55; p < 0.0001) for respiratory disease, and 5.32 (3.76-7.54; p < 0.0001) for all-cause mortality. Corresponding hazard ratios in those with both the metabolic syndrome and severe airflow limitation were 2.89 (2.34-3.58; p < 0.0001) for ischemic heart disease/heart failure, 5.98 (5.28-6.78; p < 0.0001) for respiratory disease, and 4.16 (3.50-4.95; p < 0.0001) for all-cause mortality, respectively. The metabolic syndrome explained 13% and 27% of the influence of PRISm or airflow limitation on ischemic heart disease/heart failure and all-cause mortality. Interpretation: The metabolic syndrome conferred increased risk of cardiopulmonary morbidity and mortality at all levels of lung function impairment. Funding: Danish Lung Foundation, Danish Heart Foundation, Capital Region of Copenhagen, and Boehringer Ingelheim. JV is supported by the NIHR Manchester BRC.

Quantitative analyzes of the variability in airways via four-dimensional dynamic ventilation CT in patients with chronic obstructive pulmonary disease: correlation with spirometry data and severity of airflow limitation.

Background: In chronic obstructive pulmonary disease (COPD) patients, the diagnosis and assessment of disease severity are mainly based on spirometry, which may lead to misjudgments due to poor patient compliance. Thoracic four-dimensional dynamic ventilation computed tomography (4D-CT) provides more airway data approximating true physiological function than conventional CT. We aimed to determine dynamic changes in airways to elucidate the pathological mechanism underlying COPD and predict the severity of airflow limitation in patients. Methods: Forty-two COPD patients underwent 4D-CT and spirometry. The minimum lumen diameter changed with the breathing cycle in 4th-generation airways and was continuously measured in the apical (RB1), lateral (RB4) and posterior basal segments (RB10) of the right lung. The minimum lumen diameter in the peak inspiration and peak expiration as well as the peak expiratory/peak inspiratory ratio (E/I ratio), and dynamic coefficient of variance (CV) were calculated. Results: Correlations of FEV1% with the CV of minimum lumen diameter in RB1 (ρ=-0.473, P=0.002) and in RB10 (ρ=-0.480, P=0.005) were observed, suggesting that the dynamic variability in 4th-generation airways was associated with airflow limitation in COPD patients. The CV of the minimum lumen diameter in RB1 significantly differed between the GOLD I + II and GOLD III + IV groups {8.59 [interquartile range (IQR), 6.63-14.86] vs. 14.64 (10.65-25.88), respectively; P=0.016}, suggesting that the dynamic CV in RB1 increased significantly in the GOLD III + IV group, which had worse pulmonary ventilation function. Based on the receiver operating characteristic (ROC) curve analysis, CV-RB1 predicted FEV1% <50% with an optimal cut-off of 9.43% [sensitivity 85.7%, specificity 57.1%, area under the curve (AUC) 0.717]. Conclusions: 4D-CT might be an available method to help diagnose and evaluate the severity of COPD.

Should we be screening for COPD? - looking through the lens of lung cancer screening.

INTRODUCTION: In May 2022, the US Preventive Services Task Force published their recommendation against screening for chronic obstructive pulmonary disease (COPD) in asymptomatic adults. However, we argue the routine use of spirometry in both asymptomatic and symptomatic high-risk smokers has utility. AREAS COVERED: We provide published and unpublished observations from a secondary analyses of the American College of Radiology Imaging Network (ACRIN), arm of the National Lung Screening Trial, including 18,463 high-risk current or former smokers who underwent pre-bronchodilator spirometry at baseline. According to history alone, 20% reported a prior diagnosis of 'COPD,' although only 11% (about one half), actually had airflow limitation (Diagnosed COPD) and 9% had Global Initiative for Obstructive Pulmonary Disease GOLD 0 Pre-COPD. Of the remaining 80% of 'asymptomatic' screening participants, 23% had airflow limitation (Screen-detected COPD) and 13% had preserved ratio impaired spirometry (PRISm). This means 45% of this high-risk cohort were reclassified by spirometry, and together with comorbid disease, identified subgroups where lung cancer screening efficacy could be optimized by between 2-6 fold. EXPERT OPINION: Our preliminary findings suggest lung cancer screening outcomes vary according to 'new' COPD-related spirometric-defined subgroups and that screening spirometry, together with comorbid disease, identifies those for whom lung cancer screening is mostly beneficial or potentially harmful.

Longitudinal Changes and Association of Respiratory Symptoms with Preserved Ratio Impaired Spirometry (PRISm): The Nagahama Study.

Rationale: Subjects with preserved ratio impaired spirometry (PRISm) experience increased respiratory symptoms, although they present heterogeneous characteristics. However, the longitudinal changes in these symptoms and respiratory function are not well known. Objectives: To investigate PRISm from the viewpoint of respiratory symptoms in a longitudinal, large-scale general population study. Methods: The Nagahama study included 9,789 inhabitants, and a follow-up evaluation was conducted after 5 years. Spirometry and self-administered questionnaires regarding respiratory symptoms, including prolonged cough, sputum and dyspnea, and comorbidities were conducted. Results: In total, 9,760 subjects were analyzed, and 438 subjects had PRISm. Among the subjects with PRISm, 53% presented with respiratory symptoms; dyspnea was independently associated with PRISm. Follow-up assessment revealed that 73% of the subjects with PRISm with respiratory symptoms were consistently symptomatic, whereas 39% of the asymptomatic subjects with PRISm developed respiratory symptoms within 5 years. In addition, among subjects with respiratory symptoms without airflow limitation at baseline, PRISm was a risk factor for the development of airflow limitation independent of smoking history and comorbidities. Conclusions: This study demonstrated that 53% of the subjects with PRISm had respiratory symptoms; dyspnea was a distinct characteristic of PRISm. Approximately three-fourths of the symptomatic subjects with PRISm consistently complained of respiratory symptoms within 5 years. Together with our result that PRISm itself is an independent risk factor for the development of chronic obstructive pulmonary disease among subjects with respiratory symptoms, the clinical course of subjects with PRISm with symptoms requires careful monitoring.

Association Between Oral Health and Airflow Limitation: Analysis Using a Nationwide Survey in Korea.

BACKGROUND: Although poor oral health is a common comorbidity in individuals with airflow limitation (AFL), few studies have comprehensively evaluated this association. Furthermore, the association between oral health and the severity of AFL has not been well elucidated. METHODS: Using a population-based nationwide survey, we classified individuals according to the presence or absence of AFL defined as pre-bronchodilator forced expiratory volume in 1 second/forced vital capacity < 0.7. Using multivariable logistic regression analyses, we evaluated the association between AFL severity and the number of remaining teeth; the presence of periodontitis; the Decayed, Missing, and Filled Teeth (DMFT) index; and denture wearing. RESULTS: Among the 31,839 participants, 14% had AFL. Compared with the control group, the AFL group had a higher proportion of periodontitis (88.8% vs. 79.4%), complete denture (6.2% vs. 1.6%), and high DMFT index (37.3% vs. 27.8%) (P < 0.001 for all). In multivariable analyses, denture status: removable partial denture (adjusted odds ratio [aOR], 1.12; 95% confidence interval [95% CI], 1.04-1.20) and complete denture (aOR, 1.52; 95% CI, 1.01-2.05), high DMFT index (aOR, 1.13; 95% CI, 1.02-1.24), and fewer permanent teeth (0-19; aOR, 1.32; 95% CI, 1.12-1.52) were significantly associated with AFL. Furthermore, those with severe to very severe AFL had a significantly higher proportion of complete denture (aOR, 2.41; 95% CI, 1.11-3.71) and fewer remaining teeth (0-19; aOR, 2.29; 95% CI, 1.57-3.01). CONCLUSION: Denture wearing, high DMFT index, and fewer permanent teeth are significantly associated with AFL. Furthermore, a reduced number of permanent teeth (0-19) was significantly related to the severity of AFL. Therefore, physicians should pay attention to oral health in managing patients with AFL, such as chronic obstructive pulmonary disease.