Extended NO analysis is a promising tool in different diseases where NO metabolism is altered. One single exhalation cannot give insight to the NO production in the respiratory system; rather the use of multiple exhalation flows can give the alveolar levels (C(A)NO), airway wall concentration (C(aw)NO) and the diffusion rate of NO (D(aw)NO). Increased values of C(A)NO are shown in COPD, systemic sclerosis, hepatopulmonary syndrome and in severe asthma. In asthma the C(aw)NO and D(aw)NO are increased leading to an increase in bronchial NO flux (J'(aw)NO). Low levels of J'(aw)NO are seen in cystic fibrosis, primary ciliary dyskinesia and in smoking subjects. More studies are needed to evaluate the clinical usefulness of the extended NO analysis, similar to what has been done in systemic sclerosis where a cut-off value has been identified predicting pulmonary function deterioration.

Background/Objective: Systemic inflammation is common in chronic obstructive pulmonary disease (COPD), and evidence suggests that inflammatory biomarkers can predict acute exacerbations (AECOPDs). The aim of this study was to analyse whether C-reactive protein (CRP), fibrinogen, white blood cell count (WBC), or the blood cell indices PLR (platelet-to-lymphocyte ratio), SII (systemic immune inflammation index), SIRI (systemic inflammation response index), and AISI (aggregate index of systemic inflammation) can predict future AECOPDs. Methods: In the Tools Identifying Exacerbations (TIE) cohort study, participants with spirometry-confirmed COPD were recruited from primary and secondary care in three Swedish regions and assessed during a stable phase of COPD. AECOPD frequency during the three-year follow-up was reviewed in medical records. Associations were analysed via ordinal logistic regressions. Results: Of the 571 participants, 46% had ≥1 AECOPD during follow-up, and the mean ± SD AECOPD frequency was 0.63 ± 1.2/year. In unadjusted analyses, high levels of CRP (odds ratio 1.86, 95% CI 1.29–2.67), fibrinogen (2.09, 1.38–3.16), WBCs (2.18, 1.52–3.13), SII (1.52, 1.05–2.19), SIRI (1.76, 1.23–2.52), and AISI (1.99, 1.38–2.87) were associated with a higher AECOPD frequency. After adjustment for AECOPD history, age, sex, smoking, body mass index, COPD Assessment Test score, lung function, and inhaled corticosteroid use, associations remained for high levels of CRP (adjusted odds ratio of 1.64; 95% CI of 1.08–2.49), fibrinogen (1.55; 1.07–2.24), and WBC (1.65; 1.10–2.47). Conclusions: CRP, fibrinogen, and WBC, assessed during stable-phase COPD, enhanced AECOPD prediction, whereas PLR, SII, SIRI, and AISI did not.

Background: Despite chronic obstructive pulmonary disease (COPD) being the commonest non-communicable disease in Nepal, there is limited research evidence estimating the spirometry-based burden of COPD. This study aims to estimate the prevalence of COPD and its correlates through a community-based survey in Pokhara Metropolitan City, a semi-urban area of Western Nepal. Methods: A cross-sectional household survey was conducted among 1459 adults ≥ 40 years. COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria as a post-bronchodilator ratio of forced expiratory volume in 1st second (FEV₁) to forced vital capacity (FVC) < 0.70 with the presence of symptoms. COPD was also defined by the lower limit of normal (LLN) threshold – FEV₁/FVC < LLN cut-off values with the presence of symptoms. Study participants were interviewed about sociodemographic and behavioural characteristics and respiratory symptoms. Descriptive statistics and logistic regression analysis were applied. Results: Spirometry reports were acceptable in 1438 participants. The mean age of the participants was 55 (± 10) years, and, 54% were female. The prevalence of GOLD-defined COPD was 8.5% (95% CI: 7.1– 10.0) and based on the LLN threshold of 5.4% (95% CI: 4.2– 6.6). The multivariate logistic regression showed that increasing age, low body mass index, illiterate, current or former smoker, and biomass fuel smoke increased the odds of COPD in both the definitions. Conclusion: COPD is highly prevalent at community level and often underdiagnosed. Strategies aiming at early diagnosis and treatment of COPD, especially for the elderly, illiterate, and reducing exposure to smoking and biomass fuel smoke and childhood lung infection could be effective.

Background: Elevated exhaled nitric oxide fraction at a flow rate of 50 mL·s ⁻¹ ( F ENO ₅₀ ) is an important indicator of T-helper 2-driven airway inflammation and may aid clinicians in the diagnosis and monitoring of asthma. This study aimed to derive Global Lung Function Initiative reference equations and the upper limit of normal for F ENO ₅₀ . Methods: Available individual F ENO ₅₀ data were collated and harmonised using consensus-derived variables and definitions. Data collected from individuals who met the harmonised definition of “healthy” were analysed using the generalised additive models of location, scale and shape (GAMLSS) technique. Results: Data were retrospectively collated from 34 782 individuals from 34 sites in 15 countries, of whom 8022 met the definition of healthy (19 sites, 11 countries). Overall, height, age and sex only explained 12% of the between-subject variability of F ENO ₅₀ (R ² =0.12). F _ENO device was neccessary as a predictor of F ENO ₅₀ , such that the healthy range of values and the upper limit of normal varied depending on which device was used. The range of F ENO ₅₀ values observed in healthy individuals was also very wide, and the heterogeneity was partially explained by the device used. When analysing a subset of data in which F ENO ₅₀ was measured using the same device and a stricter definition of health (n=1027), between-site heterogeneity remained. Conclusion: Available F ENO ₅₀ data collected from different sites using different protocols and devices were too variable to develop a single all-age reference equation. Further standardisation of F _ENO devices and measurement are required before population reference values might be derived.

Background: Unlike the 2014 guidelines, the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines have removed lung function from the risk assessment algorithm of patients with COPD. The aim of this investigation was to analyze the proportion of subjects who would change to a lower risk group when applying GOLD²⁰¹⁷ and determine if they exhibit different characteristics in terms of inflammation, symptoms and comorbidity compared to the subjects who would remain in a high-risk group. Subjects and methods: A total of 571 subjects with physician-diagnosed and spirometry-verified COPD were included in the present study. The data consisted of measurements of lung function, inflammatory markers, together with questionnaires that covered comorbidities, COPD symptoms and medication. Results: From group C, 53% of the subjects would be reclassified to the lower risk group A, and from group D, 47% of the subjects would be reclassified to the lower risk group B when using GOLD²⁰¹⁷ instead of GOLD²⁰¹⁴. Compared to the subjects who would remain in group D, those who would change to group B were more often men (56% vs 72%); of an older age, mean (SD), 71 (8) years vs 68 (7) years; had more primary care contact (54% vs 33%); had lower levels of blood neutrophils, geometrical mean (95% CI), 5.3 (5.0, 5.7) vs 4.6 (4.3, 4.9); reported less anxiety/depression (20% vs 34%); experienced less asthma (29% vs 46%) and had fewer symptoms according to the COPD assessment test,16 (5) vs 21 (7). All p-values were <0.05. Conclusion: The removal of spirometry from risk assessment in GOLD²⁰¹⁷ would lead to the reclassification of approximately half of the subjects in the risk groups C and D to the lower risk groups A and B. There are differences in age, gender, health care contacts, inflammation, comorbidity and symptom burden among those changing from group D to group B. The effects of reclassification and changes in eventual treatment for disease control and symptom burden need further investigation.