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.

Allergic and hypersensitivity conditions in non-specialist care: Flow diagrams to support clinical practice.

Most patients presenting with allergies are first seen by primary care health professionals. The perceived knowledge gaps and educational needs were recently assessed in response to which the LOGOGRAM Task Force was established with the remit of constructing pragmatic flow diagrams for common allergic conditions in line with an earlier EAACI proposal to develop simplified pathways for the diagnosis and management of allergic diseases in primary care. To address the lack of accessible and pragmatic guidance, we designed flow diagrams for five major clinical allergy conditions: asthma, anaphylaxis, food allergy, drug allergy, and urticaria. Existing established allergy guidelines were collected and iteratively distilled to produce five pragmatic and accessible tools to aid diagnosis and management of these common allergic problems. Ultimately, they should now be validated prospectively in primary care settings.

Cognitive dysfunction and quality of life during pollen season in children with seasonal allergic rhinitis.

BACKGROUND: Allergic rhinitis often gives rise to impaired quality of life and is believed to also affect cognitive function. We aimed to examine whether cognitive functions were impaired during grass pollen season in symptomatic allergic children and to relate the degree of impairment to quality of life and biomarkers related to stress and inflammation. METHODS: Forty-three grass pollen-allergic children (age 8-17 years) with non-satisfactory effect of medication (antihistamines and nasal steroids daily) during previous seasons were included. In addition, 26 matched non-allergic children were included as controls. Both groups performed cognitive tests (CANTAB) and completed Quality of Life questionnaires outside and during the pollen season. Blood samples were collected and analyzed for stress and inflammatory biomarkers. Pollen level was measured daily. RESULTS: Impaired cognitive function was found in spatial working memory, where the allergic group made more errors compared to the non-allergic group during pollen season, but not off-season. No significant differences could be seen between the allergic group and the controls in the other tests investigating visual memory or attention. Quality of health questionnaires revealed more symptoms and impaired quality of life in allergic compared to non-allergic children, and increased symptoms in allergic children were associated with longer reaction time for simple movement during pollen season. No differences in stress or inflammatory biomarkers could be found between the groups. CONCLUSION: Cognitive function was affected during pollen season in pollen-allergic children, and the more symptoms the allergic children had, the longer the reaction time in the cognitive tests.

Clinical characteristics of the BREATHE cohort - a real-life study on patients with asthma and COPD.

Background: The BREATHE study is a cross-sectional study of real-life patients with asthma and/or COPD in Denmark and Sweden aiming to increase the knowledge across severities and combinations of obstructive airway disease. Design: Patients with suspicion of asthma and/or COPD and healthy controls were invited to participate in the study and had a standard evaluation performed consisting of questionnaires, physical examination, FeNO and lung function, mannitol provocation test, allergy test, and collection of sputum and blood samples. A subgroup of patients and healthy controls had a bronchoscopy performed with a collection of airway samples. Results: The study population consisted of 1403 patients with obstructive airway disease (859 with asthma, 271 with COPD, 126 with concurrent asthma and COPD, 147 with other), and 89 healthy controls (smokers and non-smokers). Of patients with asthma, 54% had moderate-to-severe disease and 46% had mild disease. In patients with COPD, 82% had groups A and B, whereas 18% had groups C and D classified disease. Patients with asthma more frequently had childhood asthma, atopic dermatitis, and allergic rhinitis, compared to patients with COPD, asthma + COPD and Other, whereas FeNO levels were higher in patients with asthma and asthma + COPD compared to COPD and Other (18 ppb and 16 ppb vs 12.5 ppb and 14 ppb, p < 0.001). Patients with asthma, asthma + COPD and Other had higher sputum eosinophilia (1.5%, 1.5%, 1.2% vs 0.75%, respectively, p < 0.001) but lower sputum neutrophilia (39.3, 43.5%, 40.8% vs 66.8%, p < 0.001) compared to patients with COPD. Conclusions: The BREATHE study provides a unique database and biobank with clinical information and samples from 1403 real-life patients with asthma, COPD, and overlap representing different severities of the diseases. This research platform is highly relevant for disease phenotype- and biomarker studies aiming to describe a broad spectrum of obstructive airway diseases.

[When and how to step down asthma treatment]. / Många överbehandlas med astmamedicin - Algoritm för nedtrappning av astmaläkemedel är ett hjälpmedel för att uppnå optimal behandling.

Swedish asthma guidelines recommend treating asthma with the lowest effective dose possible. These recommendations are both hard to follow and seldom considered enough in asthma care today. As an example, combination therapy with inhaled corticosteroids (ICS) and long acting beta agonists (LABA) should only be considered if asthma control is not achieved with low to medium dose ICS daily. However, the Swedish National Board of Health and Welfare estimates that 120 000 asthma patients are overmedicated with combination therapy. Guidelines are clear in instructions of when and how to step up asthma treatment, while instructions for stepping down are not that obvious. In this article, we present an asthma treatment algorithm for step 1-3 in adults for use in clinical practice (Fig. 1), where stepping down asthma treatment is considered as an alternative. Included are also instructions of how to step down asthma treatment (Fig. 2). We conclude that stepping down is possible to do in a safe way in certain patient groups while maintaining asthma control. If possible risks are taken into consideration, stepping down asthma treatment can be done in every clinical setting.

Asthma symptoms, mannitol reactivity and exercise-induced bronchoconstriction in adolescent swimmers versus tennis players.

BACKGROUND: Strenuous physical activity at an elite level is associated with an increased risk for asthma and, in some sports, also prevalence of allergies. The aim of this study was to investigate the prevalence of asthma and allergy among elite swimmers and tennis players and compare airway hyperreactivity to mannitol and exercise. MATERIALS AND METHODS: One hundred and one adolescent swimmers and 86 tennis players answered a questionnaire about respiratory symptoms and allergy and performed mannitol challenge and sport-specific exercise challenge. Atopy was assessed and fractional exhaled nitric oxide was measured. Mannitol positivity was defined as drop in FEV1 ≥15% (ordinary criteria) and/or ß2-reversibility (≥15%) after provocation (extended criteria). A positive exercise test was defined as a drop in FEV1 ≥10% (ordinary criteria) and/or ß2-reversibility (≥15%) after provocation (extended criteria). Club cell protein (CC16) was measured in urine before and after the challenges. RESULTS: Asthma symptoms were common in both groups. More swimmers had exercise-induced symptoms (77% versus 50%) and current asthma symptoms (56% versus 38%), compared to the tennis players. More swimmers also had a positive mannitol challenge test both using ordinary (26% versus 6%) and extended criteria (43% versus 17%), while the number of positive exercise tests did not differ. After exercise (but not mannitol) challenge, CC16 level was increased in both groups, but to a higher extent in tennis players. There were no differences in atopy, rhinitis or fractional exhaled nitric oxide. CONCLUSION: We found a high prevalence of asthma among elite swimmers and tennis players and a higher frequency of current asthma and positive mannitol challenge tests among the swimmers. This indicates an unfavorable exercise environment.

Sex differences in asthma in swimmers and tennis players.

BACKGROUND: Elite athletes, independent of sport, have increased risk of developing asthma, but little is known about sex difference among adolescent athletes. OBJECTIVE: To investigate and compare sex-related differences according to symptoms and treatment of asthma, allergy, and health among elite athletes and a reference group. METHODS: Adolescent elite swimmers (n = 101), tennis players (n = 86), and a reference group (n = 1,628) responded to a questionnaire about respiratory symptoms, allergy, health behavior, psychosomatic symptoms, self- esteem, and well-being. The athletes performed a mannitol provocation and a sport-specific exercise provocation. Atopy was assessed by skin prick tests, and fractional exhaled nitric oxide was measured. RESULTS: The females reported more asthma symptoms than the males in both the reference group (29.1% vs 22.3%) and the athlete group (56.4% vs 40.2%). However, no significant differences were found in physician-diagnosed asthma or treatment with inhaled corticosteroids. More female athletes had a positive mannitol provocation result (48.7% vs 35.8% in male athletes), and more female swimmers had a positive exercise provocation result (15.1% vs 7.7% in male swimmers). The females in all groups had more psychosomatic symptoms compared with the respective males, and the males in the reference group reported higher self-esteem and felt more well-being compared with the reference group females. CONCLUSION: Overall, we found a higher prevalence of asthma symptoms in the females. However, the frequency of physician-diagnosed asthma and the prescription of inhaled corticosteroids were the same in both sexes. This finding demonstrates an insufficient diagnosis of asthma in females.

Asthma control in patients on fixed dose combination evaluated with mannitol challenge test.

Asthma is often difficult to control and it is likely that not all patients are optimally treated. This study aimed to explore asthma control in adults receiving fixed dose combination (FDC) therapy. Control of asthma was assessed using the mannitol challenge test as a monitoring tool to see if this would give additional information compared to the asthma control test (ACT). The study was an open-label, prospective study on 98 adults prescribed with FDC therapies for at least three months. 74 patients considered that their asthma was well controlled. However, 60 patients had a positive mannitol challenge test (PD15 < 635 mg), and when those with a positive response to the short-acting ß2-agonist (≥15%) after the mannitol challenge test were included, this increased to 64 patients (65%). Exploratory analysis determined that the spirometry parameters; FEV1/FVC and FEV1% of predicted, were statistically significant predictors of a positive mannitol challenge test. Co-morbid conditions such as concomitant upper airway involvement or eczema did not predict mannitol reactivity. Although most patients rated their asthma as well controlled, many provided a positive mannitol challenge test, suggesting the presence of underlying inflammation, despite treatment with fixed dose combination therapy.

ALMA, a new tool for the management of asthma patients in clinical practice: development, validation and initial clinical findings.

BACKGROUND: Several instruments have been developed for measuring asthma control, but there is still a need to provide a structure for primary care asthma reviews. AIMS: The Active Life with Asthma (ALMA) tool was developed with the aim of structuring patient visits and assessing asthma treatment in primary care. The ability of ALMA to map out the care of asthma patients was evaluated and validated. METHODS: ALMA was developed with patient and clinical expert input. Questions were generated in focus groups and the resulting tool was subsequently validated by factor analysis in 1779 patients (1116 females) of mean age 51 years (range 18-89) in primary care. RESULTS: The ALMA tool includes 19 questions, 14 of which belong to a subset assessing asthma control. In this subset, factor analysis revealed three domains (factors): physical, psychological, and environmental triggers. Correlation with the Asthma Control Questionnaire was 0.72 and the Cronbach's alpha was 0.88. The test-retest reliability was 0.93. Of the 1779 patients tested with ALMA in primary care, 62% reported chest tightness, 30% nightly awakenings and 45% asthma breakthrough despite medication. CONCLUSIONS: The ALMA tool is useful as a follow-up instrument in clinical practice to structure patient visits and assess asthma treatment in primary care. The breadth of the questions and the pragmatic use in clinical practice also make it useful as an outcome measure.

Extended diagnostic criteria used for indirect challenge testing in elite asthmatic swimmers.

UNLABELLED: The aim of the study was to investigate the prevalence of asthma with or without exercise induced symptoms among elite and elite aspiring swimmers and to compare sport specific exercise provocation with mannitol provocation. METHODS: 101 adolescent swimmers were investigated with mannitol provocation and sport specific exercise challenge test. Mannitol positivity was defined as either direct FEV(1) PD15 (ordinary criteria) or as ß(2)-reversibility ≥15% after challenge (extended criteria). A direct positive exercise test was defined as a drop in FEV(1) of 10% (ordinary criteria) or a difference in FEV of ≥15% either spontaneous, variability, or with ß2-agonist, reversibility (extended criteria). RESULTS: We found a high prevalence of mannitol and/or exercise positivity. Twenty-six swimmers were mannitol direct positive and 14 were direct exercise positive using ordinary criteria. Using extended criteria 43 were mannitol positive and 24 were exercise positive. When including reversibility and variability to define a positive test the sensitivity for current asthma with or without exercise induced symptoms increased while the specificity remained roughly unchanged. Direct positivity for mannitol and exercise poorly overlapped using ordinary criteria but improved using extended criteria. CONCLUSION: We found a high prevalence of asthma among elite swimmers. The use of variability and reversibility (liability) as additional criteria to define a positive test provided to our mind relevant information and should be considered.

Exercise but not mannitol provocation increases urinary Clara cell protein (CC16) in elite swimmers.

Elite swimmers have an increased risk of developing asthma, and exposure to chloramine is believed to be an important trigger factor. The aim of the present study was to explore pathophysiological mechanisms behind induced bronchoconstriction in swimmers exposed to chloramine, before and after swim exercise provocation as well as mannitol provocation. Urinary Clara cell protein (CC16) was used as a possible marker for epithelial stress. 101 elite aspiring swim athletes were investigated and urinary samples were collected before and 1 h after completed exercise and mannitol challenge. CC16, 11ß-prostaglandin (PG)F(2α) and leukotriene E(4) (LTE(4)) were measured. Urinary levels of CC16 were clearly increased after exercise challenge, while no reaction was seen after mannitol challenge. Similar to CC16, the level of 11ß-PGF(2α) was increased after exercise challenge, but not after mannitol challenge, while LTE(4) was reduced after exercise. There was no significant difference in urinary response between those with a negative compared to positive challenge, but a tendency of increased baseline levels of 11ß-PGF(2α) and LTE(4) in individuals with a positive mannitol challenge. The uniform increase of CC16 after swim exercise indicates that CC16 is of importance in epithelial stress, and may as such be an important pathogenic factor behind asthma development in swimmers. The changes seen in urinary levels of 11ß-PGF(2α) and LTE(4) indicate a pathophysiological role in both mannitol and exercise challenge.

Bronchodilator efficacy of tiotropium in patients with mild to moderate COPD.

AIMS: Evaluation of tiotropium efficacy in patients with mild chronic obstructive pulmonary disease (COPD) defined by the 2003 Swedish Society of Respiratory Medicine guidelines (post-bronchodilator FEV1/FVC <70%; FEV1 >60% predicted). METHODS: In this 12-week, randomised, double-blind, placebo-controlled study of tiotropium 18 mcg once daily versus placebo, respiratory function was assessed on Days 1, 15 and 85 (baseline: pre-dose Day 1). RESULTS: Mean+/-SD baseline FEV1 (% predicted) was 73.4+/-12.5 (tiotropium, n=107; placebo, n=117). Tiotropium significantly improved change from baseline in area under the curve from pre-dose to 2 hours post-dose (AUC0-2 h) FEV1 versus placebo, by 166+/-26 mL (mean+/-SE) at study end (p<0.0001). With tiotropium, there were significant increases in the change in AUC0-2 h FVC versus baseline, and trough FEV1 and FVC, versus placebo, on all test days (p<0.01). Adverse event rates were similar. CONCLUSION: Compared with placebo, tiotropium improved lung function in patients with mild COPD.