Lower airway microbiota in COPD and healthy controls.

BACKGROUND: The lower airway microbiota in patients with chronic obstructive pulmonary disease (COPD) are likely altered compared with the microbiota in healthy individuals. Information on how the microbiota is affected by smoking, use of inhaled corticosteroids (ICS) and COPD severity is still scarce. METHODS: In the MicroCOPD Study, participant characteristics were obtained through standardised questionnaires and clinical measurements at a single centre from 2012 to 2015. Protected bronchoalveolar lavage samples from 97 patients with COPD and 97 controls were paired-end sequenced with the Illumina MiSeq System. Data were analysed in QIIME 2 and R. RESULTS: Alpha-diversity was lower in patients with COPD than controls (Pielou evenness: COPD=0.76, control=0.80, p=0.004; Shannon entropy: COPD=3.98, control=4.34, p=0.01). Beta-diversity differed with smoking only in the COPD cohort (weighted UniFrac: permutational analysis of variance R2=0.04, p=0.03). Nine genera were differentially abundant between COPD and controls. Genera enriched in COPD belonged to the Firmicutes phylum. Pack years were linked to differential abundance of taxa in controls only (ANCOM-BC (Analysis of Compositions of Microbiomes with Bias Correction) log-fold difference/q-values: Haemophilus -0.05/0.048; Lachnoanaerobaculum -0.04/0.03). Oribacterium was absent in smoking patients with COPD compared with non-smoking patients (ANCOM-BC log-fold difference/q-values: -1.46/0.03). We found no associations between the microbiota and COPD severity or ICS. CONCLUSION: The lower airway microbiota is equal in richness in patients with COPD to controls, but less even. Genera from the Firmicutes phylum thrive particularly in COPD airways. Smoking has different effects on diversity and taxonomic abundance in patients with COPD compared with controls. COPD severity and ICS use were not linked to the lower airway microbiota.

Association between Covid-19 infection and platypnea-orthodeoxia syndrome.

Introduction and importance: Platypnea-orthodeoxia syndrome is defined as dyspnoea and deoxygenation when changing from a recumbent to an upright position. Post-Covid-19 sequelae can induce or exacerbate pulmonary hypertension and thereby render a previously mild and asymptomatic platypnea-orthodeoxia syndrome to manifest with new or worsening symptoms. Case presentation: The authors present the case of an 80-year-old man who following an episode of moderate-severe Covid-19 infection developed type I respiratory failure that required hospital discharge with long-term oxygen therapy. He had a background history of postural paroxysmal hypoxaemia which had previously raised the suspicion of a right-to-left shunt through either a patent foramen ovale, atrial septal defect or an intrapulmonary arteriovenous malformation. However, given the low burden of symptoms this was not explored further. Following recovery from Covid-19 infection, the patient experienced marked dyspnoea and oxygen desaturation in an upright position that was relieved by a return to a supine position. Discussion and conclusion: Persistent dyspnoea and hypoxia are common symptoms in patients who experience post-Covid-19 syndrome. However, when patients with prior moderate-to-severe Covid-19 illness present with new onset breathlessness and/or desaturation that is worsened in an upright position, platypnea-orthodeoxia syndrome should be considered.

Prevalence and impact of exercise-induced laryngeal obstruction in asthma: a study protocol for a cross-sectional and longitudinal study.

INTRODUCTION: Exercise-induced laryngeal obstruction (EILO) and exercise-induced asthma can cause troublesome respiratory symptoms that can be difficult to distinguish between. Further, there is now a growing appreciation that the two conditions may coexist, complicating the interpretation of symptoms. The primary aim of this study is to investigate the prevalence of EILO in patients with asthma. Secondary aims include evaluation of EILO treatment effects and investigation of comorbid conditions other than EILO in patients with asthma. METHODS AND ANALYSIS: The study will be conducted at Haukeland University Hospital and Voss Hospital in Western Norway, and enrol 80-120 patients with asthma and a control group of 40 patients without asthma. Recruitment started in November 2020, and data sampling will continue until March 2024. Laryngeal function will be assessed at baseline and at a 1-year follow-up, using continuous laryngoscopy during high-intensity exercise (CLE). Immediately after the EILO diagnosis is verified, patients will be treated with standardised breathing advice guided by visual biofeedback from the laryngoscope video screen. The primary outcome will be the prevalence of EILO in patients with asthma and control participants. Secondary outcomes include changes in CLE scores, asthma-related quality of life, asthma control and number of the asthma exacerbations, as assessed between baseline and the 1-year follow-up. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Regional Committee for Medical and Health Research Ethics, Western Norway, (ID number 97615). All participants will provide signed informed consent before enrolment. The results will be presented in international journals and conferences. TRIAL REGISTRATION NUMBER: NCT04593394.

Characterization of Patients in the International Severe Asthma Registry with High Steroid Exposure Who Did or Did Not Initiate Biologic Therapy.

Background: Many severe asthma patients with high oral corticosteroid exposure (HOCS) often do not initiate biologics despite being eligible. This study aimed to compare the characteristics of severe asthma patients with HOCS who did and did not initiate biologics. Methods: Baseline characteristics of patients with HOCS (long-term maintenance OCS therapy for at least 1 year, or ≥4 courses of steroid bursts in a year) from the International Severe Asthma Registry (ISAR; https://isaregistries.org/), who initiated or did not initiate biologics (anti-lgE, anti-IL5/5R or anti-IL4R), were described at the time of biologic initiation or registry enrolment. Statistical relationships were tested using Pearson's chi-squared tests for categorical variables, and t-tests for continuous variables, adjusting for potential errors in multiple comparisons. Results: Between January 2015 and February 2021, we identified 1412 adult patients with severe asthma from 19 countries that met our inclusion criteria of HOCS, of whom 996 (70.5%) initiated a biologic and 416 (29.5%) did not. The frequency of biologic initiation varied across geographical regions. Those who initiated a biologic were more likely to have higher blood eosinophil count (483 vs 399 cells/µL, p=0.003), serious infections (49.0% vs 13.3%, p<0.001), nasal polyps (35.2% vs 23.6%, p<0.001), airflow limitation (56.8% vs 51.8%, p=0.013), and uncontrolled asthma (80.8% vs 73.2%, p=0.004) despite greater conventional treatment adherence than those who did not start a biologic. Both groups had similar annual asthma exacerbation rates in the previous 12 months (5.7 vs 5.3, p=0.147). Conclusion: Around one third of severe HOCS asthma patients did not receive biologics despite a similar high burden of asthma exacerbations as those who initiated a biologic therapy. Other disease characteristics such as eosinophilic phenotype, serious infectious events, nasal polyps, airflow limitation and lack of asthma control appear to dictate biologic use.

Characteristics of hypertension and arterial stiffness in obstructive sleep apnea: A Scandinavian experience from a prospective study of 6408 normotensive and hypertensive patients.

The impact of obstructive sleep apnea (OSA) on arterial stiffness is less studied. We aimed to investigate the prevalence and covariates of increased pulse pressure (PP), a surrogate marker of arterial stiffness, in the entire study population as well as in separate analyses in normotensive and hypertensive patients. Further, we also explored the impact of smoking on brachial BP in hypertensive patients. Between 2012 and 2019, a total of 6408 participants with suspected OSA underwent a standard out-of-center respiratory polygraphy. OSA was defined by an apnea-hypopnea index (AHI) ≥15/h regardless of symptoms. PP ≥60 mmHg was used as a surrogate marker of increased arterial stiffness. Mean age was 49.3±13.7 years, 69.4% were male, and 34.5% had OSA. The prevalence of hypertension was 70.8% in OSA and 46.7% in No-OSA (AHI < 15/h) controls (P < .0001). Hypertension was controlled (clinic BP < 140/90 mmHg) in 45.5% and uncontrolled in 54.5% (P < .001). Mean PP was 50±12 mmHg in smokers and 52±12 mmHg in non-smokers (P = .001). Increased PP was found in 24.2% of the entire study population and was higher in patients with OSA compared to No-OSA group (27.5% vs 22.4%, P < .0001). In an unadjusted logistic regression model, OSA was associated with a 1.3-fold higher risk of having increased PP (95% CI 1.16-1.48, P < .001). In a multivariable-adjusted model, higher age, male sex, and history of hypertension, but not OSA (OR 0.89; 95% CI 0.77-1.02, P = .104) were associated with increased PP. In this large study of nearly 6500 participants who were referred with suspected OSA, one-third were diagnosed with OSA and a quarter had increased arterial stiffness by elevated brachial PP. Hypertension but not OSA per se was associated with increased arterial stiffness. Hypertension was highly prevalent and poorly controlled.

The lower airways microbiome and antimicrobial peptides in idiopathic pulmonary fibrosis differ from chronic obstructive pulmonary disease.

BACKGROUND: The lower airways microbiome and host immune response in chronic pulmonary diseases are incompletely understood. We aimed to investigate possible microbiome characteristics and key antimicrobial peptides and proteins in idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). METHODS: 12 IPF patients, 12 COPD patients and 12 healthy controls were sampled with oral wash (OW), protected bronchoalveolar lavage (PBAL) and right lung protected sterile brushings (rPSB). The antimicrobial peptides and proteins (AMPs), secretory leucocyte protease inhibitor (SLPI) and human beta defensins 1 and 2 (hBD-1 & hBD-2), were measured in PBAL by enzyme linked immunosorbent assay (ELISA). The V3V4 region of the bacterial 16S rDNA gene was sequenced. Bioinformatic analyses were performed with QIIME 2. RESULTS: hBD-1 levels in PBAL for IPF were lower compared with COPD. The predominant phyla in IPF were Firmicutes, Bacteroides and Actinobacteria; Proteobacteria were among top three in COPD. Differential abundance analysis at genus level showed significant differences between study groups for less abundant, mostly oropharyngeal, microbes. Alpha diversity was lower in IPF in PBAL compared to COPD (p = 0.03) and controls (p = 0.01), as well as in rPSB compared to COPD (p = 0.02) and controls (p = 0.04). Phylogenetic beta diversity showed significantly more similarity for IPF compared with COPD and controls. There were no significant correlations between alpha diversity and AMPs. CONCLUSIONS: IPF differed in microbial diversity from COPD and controls, accompanied by differences in antimicrobial peptides. Beta diversity similarity between OW and PBAL in IPF may indicate that microaspiration contributes to changes in its microbiome.

Eosinophilic and Noneosinophilic Asthma: An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort.

BACKGROUND: Phenotypic characteristics of patients with eosinophilic and noneosinophilic asthma are not well characterized in global, real-life severe asthma cohorts. RESEARCH QUESTION: What is the prevalence of eosinophilic and noneosinophilic phenotypes in the population with severe asthma, and can these phenotypes be differentiated by clinical and biomarker variables? STUDY DESIGN AND METHODS: This was an historical registry study. Adult patients with severe asthma and available blood eosinophil count (BEC) from 11 countries enrolled in the International Severe Asthma Registry (January 1, 2015-September 30, 2019) were categorized according to likelihood of eosinophilic phenotype using a predefined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic and clinical characteristics were defined at baseline (ie, 1 year before or closest to date of BEC). RESULTS: One thousand seven hundred sixteen patients with prospective data were included; 83.8% were identified as most likely (grade 3), 8.3% were identified as likely (grade 2), and 6.3% identified as least likely (grade 1) to have an eosinophilic phenotype, and 1.6% of patients showed a noneosinophilic phenotype (grade 0). Eosinophilic phenotype patients (ie, grades 2 or 3) showed later asthma onset (29.1 years vs 6.7 years; P < .001) and worse lung function (postbronchodilator % predicted FEV1, 76.1% vs 89.3%; P = .027) than those with a noneosinophilic phenotype. Patients with noneosinophilic phenotypes were more likely to be women (81.5% vs 62.9%; P = .047), to have eczema (20.8% vs 8.5%; P = .003), and to use anti-IgE (32.1% vs 13.4%; P = .004) and leukotriene receptor antagonists (50.0% vs 28.0%; P = .011) add-on therapy. INTERPRETATION: According to this multicomponent, consensus-driven, and evidence-based eosinophil gradient algorithm (using variables readily accessible in real life), the severe asthma eosinophilic phenotype was more prevalent than previously identified and was phenotypically distinct. This pragmatic gradient algorithm uses variables readily accessible in primary and specialist care, addressing inherent issues of phenotype heterogeneity and phenotype instability. Identification of treatable traits across phenotypes should improve therapeutic precision.

Complications and discomfort after research bronchoscopy in the MicroCOPD study.

BACKGROUND: Data on discomfort and complications from research bronchoscopy in chronic obstructive pulmonary disease (COPD) and asthma is limited. We present complications and discomfort occurring within a week after bronchoscopy, and investigate personal and procedural risk factors. METHODS: 239 subjects with COPD, asthma or without lung disease underwent research bronchoscopies as part of a microbiome study of the lower airways (the MicroCOPD study). Bronchoscopy was done in the supine position with oral scope insertion with the option of light conscious alfentanil sedation. Sampling consisted of protected specimen brushes, bronchoalveolar lavage, small volume lavage and for some, endobronchial biopsies. Bleeding, desaturation, cough, haemodynamic changes, dyspnoea and other events that required an unplanned intervention or early termination of bronchoscopy were prospectively recorded. Follow-up consisted of a telephone interview where subjects rated discomfort and answered questions about fever sensation and respiratory symptoms in the week following bronchoscopy. RESULTS: An unplanned intervention or early termination of bronchoscopy was required in 25.9% of bronchoscopies. Three subjects (1.3%) experienced potentially severe complications, of which all recovered without sequelae. COPD subjects experienced more dyspnoea than controls. Sedation and lower age was associated with less unplanned intervention or premature termination. About half of the subjects (47.7%) reported fever. Discomfort was associated with postprocedural fever, dread of bronchoscopy, higher score on the COPD Assessment Test and never-smoking. In subjects undergoing more than one bronchoscopy, the first bronchoscopy was often predictive for complications and postprocedural fever in the repeated bronchoscopy. CONCLUSION: Research bronchoscopies were not associated with more complications or discomfort in COPD subjects. 47.7% experienced postbronchoscopy fever sensation, which was associated with discomfort.

Prevalence of Parasomnias in Patients With Obstructive Sleep Apnea. A Registry-Based Cross-Sectional Study.

Objective: To assess the prevalence of parasomnias in relation to presence and severity of obstructive sleep apnea (OSA). We hypothesized higher parasomnia prevalence with higher OSA severity. Methods: The sample comprised 4,372 patients referred to a Norwegian university hospital with suspicion of OSA (mean age 49.1 years, 69.8% males). OSA was diagnosed and categorized by standard respiratory polygraphy (type 3 portable monitor). The patients completed a comprehensive questionnaire prior to the sleep study, including questions about different parasomnias during the last 3 months. Pearson chi-square tests explored differences according to the presence and severity of OSA. Furthermore, logistic regression analyses with the parasomnias as dependent variables and OSA severity as predictor were conducted (adjusted for sex, age, marital status, smoking, and alcohol consumption). Results: In all, 34.7% had apnea-hypopnea index (AHI) <5 (no OSA), 32.5% had AHI 5-14.9 (mild OSA), 17.4% had AHI 15-29.9 (moderate OSA), and 15.3% had AHI ≥30 (severe OSA). The overall prevalence of parasomnias was 3.3% (sleepwalking), 2.5% (sleep-related violence), 3.1% (sexual acts during sleep), 1.7% (sleep-related eating), and 43.8% (nightmares). The overall parasomnia prevalence was highest in the no OSA group. In the chi-square analyses, including all OSA groups, the prevalence of sleep-related violence and nightmares were inversely associated with OSA severity, whereas none of the other parasomnias were significantly associated with OSA severity. In adjusted logistic regression analyses the odds of sleepwalking was significantly higher in severe compared to mild OSA (OR = 2.0, 95% CI = 1.12-3.55). The other parasomnias, including sleep-related violence and nightmares, were not associated with OSA presence or severity when adjusting for sex and age. Conclusions: We found no increase in parasomnias in patients with OSA compared to those not having OSA. With the exception of sleepwalking, the parasomnias were not associated with OSA severity.

Prevalence of several somatic diseases depends on the presence and severity of obstructive sleep apnea.

STUDY OBJECTIVES: The objective was to investigate the prevalence of heart attack, angina pectoris, stroke, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, asthma and obesity in relation to the presence and severity of obstructive sleep apnea. METHODS: The sample consisted of 1887 patients, with mean age of 48.6 years (range 16-83 years), referred to a university hospital on suspicion of obstructive sleep apnea. The patients filled out a questionnaire asking whether they were previously diagnosed with the comorbidities in interest. Obstructive sleep apnea was diagnosed and categorized based on a standard respiratory polygraphic sleep study using a type 3 portable monitor. The patients' weight, height and blood pressure were measured during the consultations. RESULTS: In total, 37.9% were categorized as not having obstructive sleep apnea (Apnea-hypopnea index <5), 29.6% mild obstructive sleep apnea (Apnea-hypopnea index 5-14.9), 17.3% moderate obstructive sleep apnea (Apnea-hypopnea index 15-29.9), and 15.2% severe obstructive sleep apnea (Apnea-hypopnea index ≥30). The prevalence of heart attack, angina pectoris, hypertension, measured systolic blood pressure ≥140 mmHg, measured diastolic blood pressure ≥90 mmHg, diabetes mellitus and obesity (body mass index≥30) were higher with greater obstructive sleep apnea severity. Logistic and linear regression analyses showed that these comorbidities were positively associated with obstructive sleep apnea severity. This was not the case for stroke, chronic obstructive pulmonary disease and asthma. After adjustment for sex, age, alcohol and smoking in the logistic regression analyses, hypertension, measured systolic blood pressure ≥140 mmHg, measured diastolic blood pressure ≥90 mmHg and obesity remained positively associated with obstructive sleep apnea severity. CONCLUSIONS: A higher prevalence of heart attack, angina pectoris, hypertension, diabetes mellitus, and obesity was seen with greater obstructive sleep apnea severity. Obesity and hypertension, conditions easy to clinically assess, appear as the most central comorbidities with greater obstructive sleep apnea severity.

Associations between obstructive lung disease and symptoms of obstructive sleep apnoea in a general population.

OBJECTIVES: To examine the prevalence of self-reported symptoms of obstructive sleep apnoea (OSA) in relation to asthma, respiratory symptoms and pulmonary function. A secondary objective was to determine how sex impacted these relationships. METHODS: A random sample of all adults aged 47-48 and 71-73 years living in Bergen, Norway, were invited. Participants (3506, 69%) underwent spirometry testing and completed a questionnaire on sleep, respiratory symptoms and past medical history. OSA was defined by positive answers to questions on snoring, breathing cessations and daytime sleepiness. Current asthma was defined by ever having received a physician's diagnosis of asthma and current use of anti-asthma medication. Logistic regression analyses, including interaction analyses between sex and the different explanatory variables, were used to examine associations between OSA and current asthma, pre- and post-bronchodilator pulmonary function tests, smoking habits and respiratory symptoms. All models were adjusted for age, sex, waist-hip ratio and smoking. RESULTS: OSA was more prevalent in the middle-aged compared to the elderly (6.2% vs 3.6%), and in subjects reporting respiratory symptoms. 4.8% had OSA and 6.1% had current asthma. Current asthma and the lowest quartile of post-bronchodilator FVC were significantly associated with OSA with ORs of 2.5 (1.5, 4.2) and 1.7 (1.1, 2.7), respectively. In interaction analyses, women with post-bronchodilator FEV1 /FVC < 0.7 had an increased risk of OSA [OR of 4.1 (1.7, 9.7)] compared to women with a FEV1 /FVC ≥ 0.7. CONCLUSIONS: Current asthma was associated with increased risk of OSA. Women with chronic airflow limitation, but not men, had increased risk of OSA.

Increased severity of obstructive sleep apnea is associated with less anxiety and depression.

The objective was to investigate symptoms of depression and anxiety in relation to the presence and severity of obstructive sleep apnea (OSA) among patients referred with suspicion of OSA. The sample comprised 3770 consecutive patients with a mean age of 49.1 years; 69.7% were male. OSA was diagnosed and categorized based on a standard respiratory polygraphic sleep study using a type 3 portable monitor. Patients completed the validated Hospital Anxiety and Depression Scale (HADS) prior to the sleep study. In addition, they answered questions about whether they were currently in treatment for mental disorders and whether they had been diagnosed previously with depression. We adjusted for sex, age, smoking, alcohol consumption and obesity in the logistic regression analyses. In total, 35.1% had apnea-hypopnea index (AHI) < 5 (no OSA), 31.9% had AHI: 5-14.9 (mild OSA), 17.3% had AHI: 15-29.9 (moderate OSA) and 15.7% had AHI ≥ 30 (severe OSA). The prevalence of anxiety and depressive symptoms were significantly lower with increased OSA severity, and also when adjusting for sex, age, smoking, alcohol consumption and obesity (AHI ≥ 15 as dependent variable). Similarly, currently being in treatment for mental disorders and being diagnosed previously with depression were both associated negatively with OSA severity, with only the latter remaining significant in the fully adjusted model. Furthermore, multiple linear regressions showed that HADS anxiety and depression total scores were associated negatively with AHI. In conclusion, symptoms of anxiety and depression were associated negatively with OSA severity in these referred patients. The findings remained significant also after adjusting for several relevant confounders.

The effect of surgical and non-surgical weight loss on N-terminal pro-B-type natriuretic peptide and its relation to obstructive sleep apnea and pulmonary function.

BACKGROUND: Obesity is a major risk factor for obstructive sleep apnea, impaired pulmonary function and heart failure, but obesity is also associated with paradoxically low levels of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP). In subjects with severe obesity undergoing weight loss treatment, we assessed the associations between changes in severity of obstructive sleep apnea, pulmonary function and serum NT-proBNP levels. METHODS: One-year non-randomized controlled clinical trial. Participants, 69.6 % women, mean (SD) age 44.6 (10.8) years and body mass index (BMI) 45.1 (5.6) kg/m(2), underwent gastric bypass surgery (n = 76) or intensive lifestyle intervention (n = 63), resulting in 30 (8) % and 8 (9) % weight loss, respectively. The reference group included 30 normal weight, healthy, gender and age matched controls. Sleep recordings, arterial blood gases, pulmonary function and blood tests were assessed before and 1 year after the interventions. RESULTS: NT-proBNP concentrations increased significantly more after surgery than after lifestyle intervention. The post intervention values in both groups were significantly higher than in a normal weight healthy reference group. In the whole study population changes (∆) in NT-proBNP correlated significantly with changes in both BMI (r = -0.213) and apnea hypopnea index (AHI, r = -0.354). ∆NT-proBNP was, independent of age, gender and ∆BMI, associated with ∆AHI (beta -0.216, p = 0.021). ∆AHI was, independent of ∆BMI, significantly associated with changes in pO2 (beta -0.204), pCO2 (beta 0.199), forced vital capacity (beta -0.168) and forced expiratory volume first second (beta -0.160). CONCLUSIONS: Gastric bypass surgery was associated with a greater increase in NT-proBNP concentrations than non-surgical weight loss treatment. Reduced AHI was, independent of weight loss, associated with increased NT-proBNP levels and improved dynamic lung volumes and daytime blood gases. Clinical Trial Registration ClinicalTrials.gov NCT00273104, retrospectively registered Jan 5, 2006 (study start Dec 2005).

[a woman with recurrence of venous and arterial thrombosis]. / En kvinne med tilbakevendende arteriovenøse tromboser.

BACKGROUND: Hypercoagulability leading to arterial or venous thrombosis and embolism in patients with cancer is a known phenomenon. MATERIAL AND METHODS: We describe a 62 year old woman with a clinical course compatible with catastrophic antiphospholipid syndrome but seronegative findings and mucinous lung cancer. The case is discussed with reference to literature from a non-systematic PubMed search. RESULTS AND INTERPRETATION: Diagnoses of cerebral and cardiac infarcts, deep venous thrombosis and lung embolism led to a diagnosis of lung cancer by biopsy and positron emission tomography (PET). Early recurrence of venous and arterial thromboses or poor response to anticoagulation and antiplatelets should initiate cancer search in the assessment of such stroke patients. Especially the combination of venous and arterial thromboses should raise suspicion of cancer. PET and surgical cancer treatment should be evaluated at an early stage.

Prevalence and predictors of undiagnosed chronic obstructive pulmonary disease in a Norwegian adult general population.

OBJECTIVES: To determine the prevalence and predictors of undiagnosed chronic obstructive pulmonary disease (COPD) in Norway. METHODS: An age and gender stratified random sample of all adults aged 47-48 and 71-73 years in Bergen, Norway, were invited. The 3506 participants filled in questionnaires including symptoms of COPD, smoking, socio-economic status, self-rated health and cardiac co-morbidity. Spirometry was performed before and after inhalation of 400 microg of salbutamol. COPD was defined as post-bronchodilator forced expiratory volume in 1 s (FEV1) / forced vital capacity (FVC) < 0.7 whereas diagnosed COPD was defined as having received treatment for obstructive lung disease the last year. RESULTS: Three hundred-three persons (9%) were classified as having COPD, and the undiagnosed fraction was 66%. In multiple logistic regression analysis, including multiple imputation, predictors of undiagnosed COPD were absence of COPD symptoms [odds ratio (OR) 6.92, P = 0.001], and self-report of being in good/excellent health (OR 2.39, P = 0.005). When post-bronchodilator FEV1 was added to the analysis, undiagnosed disease was predicted by pack years [OR 1.21 (1.01-1.47) per 10 pack-year increase, P = 0.043], and close to normal lung function [OR 1.48 (1.22-1.80) per 10% increase in post-bronchodilator FEV1 % predicted, P < 0.001]. Anthropometrical variables, socio-economic status and cardiac co-morbidity were not associated with having undiagnosed COPD. CONCLUSION: Two out of three COPD patients in Norway are undiagnosed. Risk factors for being undiagnosed are moderate reduction in lung function, absence of COPD symptoms and self-report of being in good health.

Bronchodilator reversibility testing in an adult general population; the importance of smoking and anthropometrical variables on the response to a beta2-agonist.

Normative cut-off values for the bronchodilator reversibility test are published neglecting factors that may influence the test result other than disease. The objective of this cross-sectional study of a general population was to examine how a salbutamol reversibility test response is depending on anthropometrical variables and smoking. An age and gender stratified random sample of all adults aged 47-48 and 71-73 years living in Bergen, Norway, was invited. The 3506 attendants (69%) filled in a questionnaire and performed spirometry before and after inhalation of 400 microg salbutamol. The mean (SD) absolute FEV(1) bronchodilator response, the change in % predicted, and the change in % initial among middle-aged were 71 (122) ml, 2.0 (3.3)%, and 2.4 (4.1)%, and in the elderly 64 (113) ml, 2.4 (4.3)% and 3.3 (5.9)%, respectively. In a multiple linear regression analysis including adjustment for the initial FEV1 in % predicted, smoking and pack-years were negatively correlated to all indices. Current smoking was considerably more important than past smoking. Female gender, old age, and BMI were positively correlated with the percentage change indices, but the correlation with BMI decreased with increasing heights. These trends were unchanged after excluding subjects with obstructive lung disease or coronary heart disease. This study demonstrates that smoking habits predict all indices expressing the salbutamol bronchodilator response among middle-aged and elderly from a general population. Also, the change in % predicted and the change in % initial indices are dependent on anthropometrical variables. However, although smoking and anthropometrical variables, as well as level of lung function predict the response to inhaled beta2-agonists, these factors explain only 7-16% of the total variation of the measurement indices, and seem therefore of minor importance to the interpretation of the test result.

Factors determining performance of bronchodilator reversibility tests in middle-aged and elderly.

Knowledge of the factors determining the performance of bronchodilator reversibility testing in a general population is lacking. Random samples of all adults aged 47-48 and 71-73 years living in Bergen, Norway, were invited to a cross-sectional study. Altogether 3506 subjects attended (69%). Test quality predictors were examined through multiple logistic regression analyses including gender, age, body mass, educational level, smoking history, respiratory symptoms, and in the elderly cohort cognitive level. Among the participants, 1.6% refused to inhale salbutamol, 2.5% failed the initial spirometry according to the ATS guidelines, and 1.3% failed the post-bronchodilator spirometry. Old age and body mass index > 30 kg/m2 were independent risk factors for an unsuccessful initial spirometry, and never smoking and respiratory symptoms were risk factors for failing the post-bronchodilator spirometry. Cognitive impairment in the elderly was a risk factor for failing both the initial- and post-bronchodilator spirometry. The median number of forced expirations was 7 in subjects obtaining an acceptable reversibility test. One third of these participants needed > or = 8 attempts, with independent predicting factors being old age, Little formal education and never smoking. Although reversibility testing becomes increasingly difficult with age, reliable data are obtained in a vast majority (94%) of subjects in our community study.