Relationship between early life asthma and chronic airway disease in adult life - in search for disease trajectories over the life span- the RELATE study based on the Kongsberg cohort.

BACKGROUND: Chronic airway disease in adults may have its origin in early life. The purpose of this study is to investigate the long-term prognosis of severe childhood asthma in search for an association between asthma in early life and obstructive lung disease in adulthood. METHODS: This study is based on the Kongsberg cohort, which includes approximately 5000 children with severe asthma with a 4-month stay at the asthma care facility in Kongsberg, Norway during the years 1950 to 1979. An on average 60-year observational study based on a follow-up examination will be performed including questionnaires, blood samples, and tests of lung function and bronchial responsiveness. Blood samples will be stored in a biobank. In addition, we will conduct further analyses of the cohort based on nationwide register data, including socio-economic parameters and mortality. DISCUSSION: Chronic airway disease is associated with substantial burden for both the individual patient and society. Our knowledge of early life origins of chronic airway disease later in life has been increasing in recent decades but is still limited. By exploring early life risk factors for chronic airway disease in adulthood, we may gain insights paving the way for future reduction in the burden of chronic airway diseases.

COPD patients prescribed inhaled corticosteroid in primary care: time for re-assessment based on exacerbation rate and blood eosinophils?

BACKGROUND AND OBJECTIVE: Inhaled corticosteroid (ICS) therapy for COPD should be guided by exacerbations and blood-eosinophils according to the GOLD 2020 strategy document. In the present study, we applied these recent recommendations in a large cohort of COPD patients recruited from general practice. METHODS: The participating general practitioners (n = 144) recruited patients with a diagnosis of COPD currently prescribed ICS and reported data on exacerbation history and blood-eosinophils. Clinical variables were compared using two-sample t-tests. RESULTS: The study cohort comprised 1,567 COPD patients (44% males and mean age 72 years). In the past 12 months, 849 (54%) of the COPD patients currently prescribed ICS had no exacerbation, whereas 383 (24%) and 328 (21%) patients, respectively, had a history of one exacerbation and two or more exacerbations. Compared to patients with one or no exacerbation, patients with ≥ 2 exacerbations (21%) per year reported more dyspnea (p < 0.001) and had higher degree of airflow obstruction (p < 0.001). Among patients with no and at least one exacerbation within the preceding 12 months, 30% and 26%, respectively, had a blood-eosinophil count ≥ 0.3 × 109/L. In patients with two or more exacerbations within the last 12 months, 77% had a blood-eosinophil count of ≥ 0.1 × 109/L. Furthermore, 166 patients (11%) had at least one hospital admission due to COPD exacerbation, and a blood-eosinophil count of ≥ 0.1 × 109/L. CONCLUSION: This study of a large cohort of COPD patients currently prescribed inhaled corticosteroids suggests the need for re-evaluating the management strategy to increase benefit and reduce adverse effects of ICS treatment in COPD patients managed in primary care.

Characteristics of COPD Patients Prescribed ICS Managed in General Practice vs. Secondary Care.

Inhaled corticosteroids (ICS) for COPD have been much debated. Our aim was to investigate characteristics of ICS prescribed COPD patients managed only in general practice compared to those also managed in secondary care. Participating general practitioners recruited patients with COPD (ICPC 2nd ed. code R95) currently prescribed ICS (ACT code R03AK and R03BA). Data on demographics, comorbidities, smoking habits, spirometry, dyspnea score and exacerbation history were retrieved from medical records. Logistic regression analysis was applied to detect predictors associated with management in secondary care. 2,279 COPD patients (45% males and mean age 71 years) were recruited in primary care. Compared to patients managed in primary care only (n = 1,179), patients also managed in secondary care (n = 560) were younger (p = 0.013), had lower BMI, more life-time tobacco exposure (p = 0.03), more exacerbations (p < 0.001) and hospitalizations (p < 0.001) and lower FEV1/FVC-ratio (0.59 versus 0.52, respectively). Compared to patients managed in only primary care, logistic regression analysis revealed that management also in secondary care was associated to MRC-score ≥3 (OR 2.70; 95% CI 1.50-4.86; p = 0.001), FEV1%pred (OR 0.98; 95% CI 0.95 to 0.99; p = 0.036), and systemic corticosteroids for COPD exacerbation (OR 1.44; 95% CI 1.10-1.89; p = 0.008). In COPD patients prescribed ICS recruited in primary care, patients also managed in secondary care had more respiratory symptoms, lower lung function and exacerbations treated with systemic corticosteroids indicating that the most severe COPD patients, in general, are referred for specialist care.

COPD patients prescribed inhaled corticosteroid in general practice: Based on disease characteristics according to guidelines?

In a primary care setting, our aim was to investigate characteristics of patients classified as having chronic obstructive pulmonary disease (COPD) and currently being prescribed inhaled corticosteroids (ICSs). The electronic patient record system in each participating general practice was searched for patients coded as COPD (ICPC, Second Edition code R95) and treated with ICS (ACT code R03AK and R03BA, that is, ICS in combination with a long-acting ß2-agonist) or ICS as monotherapy. Data, if available, on demographics, smoking habits, spirometry, COPD medication, symptom score, blood eosinophils, co-morbidity and exacerbation history were retrieved from the medical records for all identified cases. Of all patients registered in the 138 participating general practices, 12.560 (3%) were coded as COPD, of whom 32% were prescribed ICS. The final study sample comprised 2.289 COPD patients currently prescribed ICS (98% also prescribed long-acting ß2-agonist), with 24% being coded as both COPD and asthma. Post-bronchodilator spirometry was available in 79% (mean forced expiratory volume in 1 second 60% pred (standard deviation (SD) 23.3)), symptom severity score in 53% (mean Medical Research Council score 2.7 (SD 1.1)) and 56% of the COPD patients had had no exacerbation in the previous year (and 45% not within the 2 previous years). Blood eosinophils were measured in 67% of the patients. Information on severity of airflow limitation was missing in 15% of the patients, and the combined information on symptom severity and exacerbation history was missing in in 46%. Most of the patients (74%) were managed only by their general practitioner. Although only one-third of the COPD patients were prescribed ICSs, our findings from this study of a large cohort of patients prescribed ICSs for COPD in general practice suggest that more detailed assessment of diagnosis and disease characteristics is likely to improve the risk-benefit ratio of maintenance therapy with ICSs in COPD patients managed in primary care.

Characteristics of Adults With Severe Asthma in Childhood: A 60-Year Follow-up Study.

BACKGROUND: Childhood asthma is a prevalent condition with potential impact on adult life. RESEARCH QUESTION: In a 60-year follow-up study of adults with a history of severe childhood asthma, what are the potential differences in characteristics between individuals with persistent asthma and asthma remission in adulthood? STUDY DESIGN AND METHODS: Danish adults with a history of childhood asthma and a 4-month stay in at an asthma care facility in Kongsberg, Norway (1950-1979) in childhood were included. Recruitment was carried out through social media and personal invitation letters. Participants completed questionnaires and underwent spirometry, bronchial provocation, and bronchodilator reversibility and blood tests. Asthma remission was defined as no use of asthma medication and no asthma symptoms within the past 12 months, with the remaining participants being classified as having current asthma. RESULTS: Among 1,394 eligible participants, 232 participants completed the follow-up. Ninety percent had current asthma, of whom 26% reported exacerbations in the past year. Only 16% of all the participants were managed in secondary care. Common comorbidities were allergic rhinitis (60%), hypertension (21%), eczema (16%), and cataract (8%). Compared with participants in remission, participants with persistent asthma showed higher total IgE (P = .03) and both lower FEV1 % predicted (P = .03) and FEV1 to FVC ratio (P < .001), as well as numerically higher fractional exhaled nitric oxide and blood eosinophil count. INTERPRETATION: Our 60-year follow-up study of adults with a history of severe childhood asthma revealed that nine of 10 participants still had current asthma. Persistent asthma was associated with lower lung function and higher levels of type 2 inflammatory biomarkers compared with asthma remission.

Inhaled Corticosteroid Exposure and Risk of Cataract in Patients with Asthma and COPD: A Systematic Review and Meta-Analysis.

Purpose: Both systemic and inhaled corticosteroids may increase the risk of cataract in patients with both chronic obstructive pulmonary disease (COPD) and asthma. Our aim was to assess the degree of association between cataract and corticosteroid exposure in patients with asthma and COPD. Methods: A systematic literature review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The odds ratio estimates were extracted from each article. A random effects model was applied for estimate pooling in separate meta-analyses according to study design. Meta-regression was performed to assess the dose-response relationship between corticosteroid exposure and the risk of cataract development. Results: A total of 19 studies met the criteria for inclusion in this review, of which 12 studies provided effect estimates for pooled analyses. All but one of the included observational studies reported a significant association between use of corticosteroids and cataract development in cohorts of asthma and/or COPD patients. Pooled analyses revealed on average a doubled risk of cataract in corticosteroid-exposed asthma and COPD patients. Studies have shown that daily high-dose inhaled corticosteroid (ICS) ≥ 1000 µg is associated with a significant risk of developing cataract and by that predispose to subsequent cataract surgery, although one study showed that systemic corticosteroids increase cataract risk more than ICS. Conclusion: ICS treatment in asthma and COPD patients is a risk factor for cataract development. Our results emphasize a previously underestimated potential long-term risk of treatment with ICS and underline the importance of targeting ICS treatment, and not least dosing, to improve the risk-benefit ratio of maintenance treatment in both asthma and COPD.

Magnesium sulfate treatment for acute severe asthma in adults-a systematic review and meta-analysis.

Introduction: Add-on magnesium sulfate (MgSO4) for refractory asthma exacerbation has been much debated. The aim of this review and meta-analysis is, therefore, to provide an update on the current evidence for the efficacy of MgSO4 in exacerbations of asthma in adults refractory to standard of care treatment. Methods: A systematic review was performed in accordance with the PRISMA guidelines. The search was performed in the PubMed database (updated April 2023). For the meta-analysis, a random-effects model was applied using the metaphor package for RStudio (RStudio, Inc.). Results: A total of 17 randomized controlled trials were included. Three of the nine studies addressing treatment with intravenous (IV) MgSO4 found a significant effect on lung function compared to placebo. Of the eight studies investigating hospital admission rate, only two found a significant effect of MgSO4. Six of the nine studies investigating treatment with nebulized MgSO4 compared to placebo found a favorable effect on forced expiratory volume in 1. second (FEV1) and peak expiratory flow rate (PEF). Only two of the five studies investigating the effect on hospital admission rate found an effect of MgSO4. Comparing effect sizes in a meta-analysis revealed a greater effect on PEF in asthma patients treated with nebulized MgSO4 (MD, 23.57; 95% CI, -2.48 to 49.62, p < 0.01) compared to placebo. The analysis of patients treated with i.v. MgSO4 compared to placebo showed no statistically significant difference (MD, 5.49; 95% CI, -18.67 to 29.65, p = 0.10). Conclusion: Up to two out of three studies revealed an effect of MgSO4 treatment for asthma exacerbation when assessed by FEV1/PEF, but fewer studies were positive for the outcome of hospital admissions.

Comparison of Characteristics Between ICS-Treated COPD Patients and ICS-Treated COPD Patients with Concomitant Asthma: A Study in Primary Care.

Background and Objective: Inhaled corticosteroids (ICS) for COPD has been much debated. Our aim was to identify characteristics associated with prescribing ICS for patients with COPD alone compared to those with concomitant asthma in general practice. Patients and Methods: Participating general practitioners (GPs) (n=144) recruited patients with COPD (ICPC 2nd ed. code R95) currently prescribed ICS (ACT code R03AK and R03BA). Data, if available, on demographics, smoking habits, spirometry, COPD medication, dyspnea score, and exacerbation history were retrieved from the medical records. Logistic regression analysis was used to identify possible differences in characteristics between patients with COPD alone compared to those having a concomitant diagnosis of asthma. Results: A total of 2.289 (45% males) COPD patients on ICS were recruited. Compared to patients with COPD alone (n=1.749), those with COPD and concomitant asthma (n=540) were younger (p<0.001), had higher BMI, higher FEV1/FVC ratio, higher blood eosinophil count and less life-time tobacco exposure (36 and 26 pack-years, respectively). Compared to COPD alone, logistic regression analysis showed that COPD with concomitant asthma was significantly associated to age (OR 0.94; CI 0.92 to 0.97; p<0.001), pack-years of smoking (OR 0.98; CI 0.97 to 0.99; p<0.001), %pred (OR 1.02; CI 1.00 to 1.03; p=0.005), and doctor-diagnosed depression (OR 2.59; CI 1.20 to 5.58; p=0.015). Conclusion: In COPD patients currently prescribed ICS, the presence of concomitant asthma was associated with being younger, having less tobacco exposure, more preserved lung function and a higher likelihood of doctor-diagnosed depression compared to COPD alone.

Early life insults as determinants of chronic obstructive pulmonary disease in adult life.

Background: Early life events may predispose to the development of chronic lung disease in adulthood. Aim: To provide an update on current knowledge of early nongenetic origins of COPD. Materials and methods: Systematic literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: A total of 16 studies, comprising 69,365 individuals, met the predefined criteria and were included in the present review. Studies have shown that in utero tobacco exposure, low birth weight, preterm birth, and respiratory diseases, primarily asthma and pneumonia, in early childhood are associated with lung function impairment later in childhood, and by that predispose to subsequent development of COPD, although the causal association between childhood respiratory diseases and COPD has been questioned in one study. Environmental tobacco exposure has also been shown to have negative impact on lung function in childhood possibly leading to COPD in adulthood, although it is at present not possible to clearly distinguish between the impact of active and the environmental tobacco exposure on subsequent development of COPD. Conclusion: Tobacco exposure in utero and early life is a risk factor for subsequent development of COPD. Furthermore, low birth weight, lower respiratory tract infections and asthma, including wheezy bronchitis, in childhood also seem to be important determinants for later development of COPD. Early life insults may, therefore, be crucial to COPD development.