Effectiveness of pulmonary rehabilitation at high-altitude compared to sea-level in adults with severe refractory asthma.

BACKGROUND: Beneficial effects of pulmonary rehabilitation at high-altitude (HAPR) in patients with severe refractory asthma have been reported earlier, but evidence for the effectiveness is limited. AIM: To investigate the effectiveness of high-altitude pulmonary rehabilitation to comparable treatment at sea-level (LAPR) on patient outcome parameters. METHODS: Adults with severe refractory asthma living in The Netherlands were included. Treatment consisted of a 12-week personalized multidisciplinary rehabilitation program either at high-altitude (Davos Switzerland) (n = 93) or in a tertiary lung center at sea-level in The Netherlands (n = 45). At baseline, after treatment, and during 12 months follow-up asthma related quality of life (AQLQ), asthma control (ACQ), pulmonary function and OCS-dose were assessed. Patients could not be randomized resulting in different asthma populations. Groups were compared using linear regression analysis (ANCOVA) adjusted for baseline values, in addition to age, atopy, smoking history, BMI and gender. RESULTS: After treatment, and at 12 months follow-up, improved AQLQ(0.92,p < 0.001 and 0.82,p = 0.001, respectively), ACQ(-0.87,p < 0.001 and -0.69,p = 0.008, respectively) and lower maintenance OCS dose (Unadjusted linear regression analysis-5.29 mg, p = 0.003 and Crude Odds Ratio-1.67, p = 0.003, respectively) were observed in the HAPR-group compared to the LAPR group. Patients receiving HAPR also had less asthma exacerbations (≥1 exacerbation: 20% vs 60%,p < 0.001) and showed improvement in lung function (%predFEV1 3.4%,p = 0.014) compared to the LAPR group, but at 12 months no differences between groups were observed. CONCLUSION: HAPR resulted in a larger improvement in patient outcome parameters compared to LAPR, on the long run the improvement in patient reported symptoms and lower maintenance OCS-dose persists. Underlying factors that explain this observed effect need to be investigated.

Predictors of benefit from high-altitude climate therapy in adults with severe asthma.

BACKGROUND: High-altitude climate therapy has been shown to benefit patients with severe asthma but it is not known which patients benefit most from this treatment. In the current study we aimed to identify clinical, functional and inflammatory predictors of favourable outcome of high-altitude climate therapy. METHODS: This is a secondary analysis of a prospective cohort including 136 adult patients with a diagnosis of severe refractory asthma, referred to the Dutch Asthma Centre in Davos (1600 metres above sea level), Switzerland. They had assessments of medication usage, asthma-related quality of life (Asthma-related Quality of Life Questionnaire, AQLQ), asthma control, body mass index (BMI), sino-nasal symptoms, fatigue, lung function (forced expiratory volume in one second, FEV1), exercise tolerance, allergy and inflammation (fraction of exhaled nitric oxide, blood eosinophils) at entry and after 12 weeks of treatment. Five clinically relevant outcomes were considered: AQLQ, oral corticosteroid dose, FEV1, body mass index and blood eosinophils. Independent predictors of beneficial outcome were identified by multiple linear regression analysis. RESULTS: Lower blood eosinophil counts (p < 0.01), younger age (p = 0.02) and poorer asthma control (p < 0.01) were independently associated with greater reduction in the dose of oral corticosteroids. Lower fatigue score at baseline (p = 0.01) was associated with greater weight loss (reduction in BMI). Higher levels of total IgE at baseline (p < 0.01), and higher doses of inhaled corticosteroids (p = 0.03) were associated with greater decreases in blood eosinophils. There were no predictors for improvement in AQLQ or FEV1. CONCLUSIONS: The beneficial effect of high-altitude climate therapy in adults with severe asthma can be predicted by patient characteristics, such as age, blood eosinophils and degree of asthma control before admission.

High-altitude treatment: a therapeutic option for patients with severe, refractory asthma?

High-altitude treatment has been applied for more than a century in the treatment of pulmonary diseases including asthma. Many uncontrolled and controlled studies have shown its beneficial effects in children and adolescents with house dust mite allergic asthma. A recent study also showed an improvement in markers of airway inflammation in adult patients with severe intrinsic asthma, suggesting that factors other than HDM avoidance may contribute to the beneficial influence of the high-altitude climate therapy on asthma. The dry mountain climate not only has decreased levels of mite allergens but also decreased levels of pollens, fungal spores and air pollution, as well as high exposure to UV light with immunomodulatory and anti-inflammatory effects. Treatments targeting environmental control have never been investigated systematically in severe asthma, which is surprising, as environmental factors have been recognized as important contributors to asthma severity for many years and more evidence has been accumulating ever since. Preliminary evidence shows the beneficial effects of high-altitude treatment in patients with severe refractory asthma on symptoms, lung function and oral corticosteroid requirement, irrespective of atopic status. In this narrative review, we will discuss why high-altitude treatment might be a promising therapeutic option for patients who suffer from this disabling disease.

Clinical evaluation of the effect of anti-allergic mattress covers in patients with moderate to severe asthma and house dust mite allergy: a randomised double blind placebo controlled study.

BACKGROUND: The use of anti-allergic mattress covers in patients with asthma can result in a large reduction in the level of house dust mite allergen in dust samples. Apart from a reduction in histamine induced bronchial hyperresponsiveness, there are few data on the effect of mattress covers on clinical efficacy and quality of life in patients with moderate to severe asthma. METHODS: Thirty patients with asthma and house dust mite allergy were studied in a randomised, double blind, placebo controlled study. Before and after using anti-allergic covers for 1 year, dust was collected from the mattresses to determine concentrations of Dermatophagoides pteronyssinus (Der p 1), and bronchial hyperresponsiveness and quality of life were measured. The patients scored their symptoms (lungs and nose), morning and evening peak flow values, and rescue medication for 14 days before and after the intervention period. RESULTS: There was a significant reduction in the concentration of Der p 1 in the dust collected from the mattresses in the actively treated group after 1 year compared with before treatment; no change was found in the placebo group. In both the actively treated and placebo groups there was no significant improvement in PC(20) histamine. Quality of life improved similarly in both groups. The symptom score of the lower airways did not significantly change in either group. A significant decrease in nasal symptom score was seen in the actively treated group compared with before treatment, but there was no significant difference between the groups. No changes in morning and evening peak flow values, peak flow variability, nor in the use of rescue medication were found in either group. CONCLUSION: The use of anti-allergic mattress covers results in significant reductions in Der p 1 concentrations in carpet-free bedrooms. However, in patients with moderate to severe asthma, airways hyperresponsiveness and clinical parameters are not affected by this effective allergen avoidance.

The effect of anti-allergic mattress encasings on house dust mite-induced early- and late-airway reactions in asthmatic patients. A double-blind, placebo-controlled study.

BACKGROUND: Anti-allergic mattress encasing may provide clinical benefit in asthmatic patients. However, the effect of mattress encasings on allergen-specific parameters, such as bronchial reactions to house dust mite (HDM) challenge, is not clear. OBJECTIVE: To investigate the effect of anti-allergic mattress encasings on allergen sensitivity in patients with moderate to severe asthma. METHODS: Twenty-seven patients with asthma and HDM allergy were studied in a double-blind, placebo-controlled study. Concentrations of Dermatophagoides pteronyssinus (Der p 1) were measured in mattress dust before and after 1 year of treatment; bronchial histamine challenge, bronchial challenge with HDM and intradermal skin challenges with HDM were performed. The number of eosinophils in peripheral blood was assessed. RESULTS: In the active group, but not in the placebo group, there was a significant reduction in Der p 1 concentration in the dust collected from the mattresses after 1 year of treatment compared to before. There was a significant difference between the groups with respect to HDM-induced early-reaction (ER) in the airways and the number of blood eosinophils, which reflected an increase in ER and eosinophils in the placebo group without significant change in the active group. No significant improvement in PC20 histamine, late-reaction (LR) and skin tests was found in either groups. CONCLUSION: Our data suggest that encasings protect against a further increase in allergen sensitivity in asthmatic patients, so their use should be recommended.

Multivariable assessment of the 6-min walking test in patients with chronic obstructive pulmonary disease.

Functional exercise tolerance in patients with chronic obstructive pulmonary disease (COPD) is often assessed by the 6-min walking test (6MWT). To assess if the use of multiple factors adds to walking distance in describing performance in the 6MWT, an exploratory factor analysis was performed on physiological measurements and dyspnea ratings recorded during testing. Eighty-three patients with mild to severe COPD performed repeated 6MWTs before inpatient pulmonary rehabilitation. Factor analysis on 15 variables yielded a stable four-factor structure explaining 78.4% of the total variance. Recorded heart rate variables contributed to factor 1 (heart rate pattern), walking distance, heart rate increase, and decrease contributed to factor 2 (endurance capacity), oxygen desaturation variables contributed to factor 3 (impairment of oxygen transport), and dyspnea and effort variables contributed to factor 4 (perceived symptoms). Walking distance decreased in half of the 53 patients measured posttreatment, but self-perceived change in exercise tolerance improved in 84% and was explained by change in walking distance, by less desaturation, and by less dyspnea (R(2) = 0.55, p = 0.005). Qualitative analysis showed that 29 of 53 patients improved in three or four factors. Performance in the 6MWT can be described with four statistically independent and clinically interpretable factors. Because clinically relevant changes consist of more than only walking distance, assessment of functional exercise tolerance in patients with COPD improves by reporting multiple variables.

Characteristics and diagnostic significance of spontaneous wheezing in children with asthma: results of continuous in vivo sound recording.

The characteristics and diagnostics of wheezing during induced airway obstruction are well documented. The present study addressed (a) the characteristics of spontaneous wheezing with respect to a possible distinction between wheezes during in vivo versus induced airway obstruction, and (b) the relationship between in vivo wheezing and fluctuations in peak expiratory flow (PEF). Tracheal sounds were continuously recorded from 50 children and adolescents with asthma and 10 without asthma in the home environment. Wheezes underwent a qualitative analysis, including their concomitant sound frequencies. Presence of wheezing was scored by two examiners independently and was related to PEF. Spontaneous wheeze varied from solitary rhonchi to prolonged rhythms of loud stridor, and resembled the "induced" wheezes recorded previously. Power spectra showed that the spectral contents (frequency distribution) were comparable, although the in vivo patterns were more prolonged in duration. The diagnostic sensitivity and specificity of wheezing for a reduction in PEF of >20% were 88% and 92%, respectively. It was concluded that in vivo wheeze resembled induced wheeze and was a diagnostically reliable symptom with respect to asthma exacerbations.

Cough as the ambiguous indicator of airway obstruction in asthma.

This study tested the hypothesis that cough frequency during induced airway obstruction in children and adolescents with asthma relates significantly to other symptoms. The second hypothesis was that cough during remission may often be a conditioned or voluntary response. In experiment 1, tracheal sounds were recorded from 30 participants with asthma during a histamine challenge test. In experiment 2, tracheal sounds were recorded from 30 participants with and 30 without asthma during a standardized physical exercise task. Cough and respiratory wheeze were assessed from the sound records by two examiners independently. The results showed that cough during airway obstruction did not relate to other variables. Only the second hypothesis was supported. In both experiments the frequency of cough was independent of lung function (forced expiratory volume in 1 sec [FEV1]), wheezing, dyspnea, and severity of asthma. The percentage of participants with asthma who coughed in experiment 1 increased from 21% (baseline) to 71% after histamine inhalation. During experiment 2, the cough percentage increased from 52% to 69% in asthmatics, and from zero to 57% in controls. It was concluded that cough in asthma is not diagnostically useful for assessment of airway obstruction. Excessive baseline cough among asthmatics could be the result of acquired responses to anticipated exercise-induced symptoms.

Diagnostics of spontaneous cough in childhood asthma: results of continuous tracheal sound recording in the homes of children.

Spontaneous cough is a symptom with diffuse diagnostic significance for childhood asthma. Information on the interrelations between presence/frequency of cough and other symptoms of asthma are not available to the physician. Tracheal sounds were continuously recorded in the homes of 60 children with and 30 without asthma, at 72 and 24 h, respectively. Presence and frequency of cough and presence of wheeze were scored by trained examiners. Wheeze was used to indicate airway obstruction during hours when peak expiratory flow (PEF) values were not available. PEF and self-reported dyspnea were assessed every 4 h. Results showed that asthmatics coughed significantly more often than control subjects during exacerbations, but not during remission. The highest diagnostic sensitivity percentages of cough were 72% for wheeze and 69% for a reduction in PEF > 20%. However, the diagnostic specificity was poor, 41% for wheeze and 34% for a reduction in PEF > 20%. Cough and dyspnea were independent. Three children did not cough during exacerbations. Persistent, isolated cough was observed in two children. It was concluded that spontaneous cough is modestly predictive of asthmatic exacerbations, but not of a diagnosis of asthma or severity of asthma.

Allergen-induced changes in airway responsiveness are related to baseline airway responsiveness.

In the literature, bronchial allergen challenge is usually reported to result in an increase in histamine-induced airway responsiveness (AR). The present study investigated the relation between baseline AR and allergen-induced changes in AR. The effect of allergen challenge on AR was investigated in 21 atopic asthmatic patients. Allergen challenge resulted in a significant decrease in PC20 histamine after 24 h. When the group was divided into three subgroups according to baseline PC20 histamine, a significant decrease in PC20 histamine was found only in patients with relatively high baseline PC20 histamine (groups 1 and 2). A significant inverse correlation was found between baseline PC20 and allergen-induced PC20 histamine. The effect of repeated allergen challenge on AR was studied in eight patients. The first allergen challenge resulted in a significant decrease in PC20 histamine; no further decrease in mean PC20 histamine was seen after the second allergen challenge. These results suggest that allergen-induced changes in AR occur mainly in patients with relatively high baseline PC20 values. Once an increase in AR is induced, further allergen challenge does not always result in further increase in AR.

Characteristics of wheeze during histamine-induced airways obstruction in children with asthma.

BACKGROUND: An automated system has been developed for the detection of sound patterns suggestive of airways obstruction in long term recordings. The first step, presented here, was tracheal sound recording during histamine-induced airways obstruction. METHODS: The tracheal sounds of 29 children aged 8-19 years with asthma were recorded during airways obstruction caused by histamine inhalation using a system for continuous respiratory telemetry and computer analysis. Sound patterns were analysed, classified, and related to airways obstruction measured by lung function tests based on the forced expiratory volume in one second (FEV1). RESULTS: Five sound patterns were identified, one dominant sensitive and four specific to a fall in FEV1 of > 20%. The presence of at least one of three specific sound patterns during unforced respiration predicted a fall in FEV1 of > 20% in 87.5% of the subjects. The inspiratory and expiratory sound patterns were almost equally informative of airways obstruction. CONCLUSIONS: Wheezes can be differentiated with more precision than is currently accepted. Tracheal sound patterns are sensitive and specific predictors of histamine-induced airways obstruction. These patterns are neither invariably nor proportionally related to the results of lung function testing. However, they can be used for detection of airways obstruction on the basis of their presence or absence.

Lack of effect of cetirizine on early and late asthmatic response after allergen challenge.

BACKGROUND: Cetirizine hydrochloride has proved effective in reducing allergic symptoms and can inhibit the infiltration of eosinophils in allergic late-phase responses in the skin. Because eosinophils are likely to play an important role in allergic late-phase reactions, we studied the effect of cetirizine on early and late asthmatic reactions and on levels of eosinophil cationic protein (ECP) in the blood after allergen challenge. METHODS: The effect of 15 mg cetirizine given twice daily was studied in 16 patients allergic to house dust mites in a double-blind, placebo-controlled study. Patients were treated for 3 weeks. Before and after treatment, bronchial challenges with house-dust mites were performed. Blood ECP levels were measured 6 hours after challenge. Methacholine provocation was performed 72 hours before and 24 hours after each challenge. RESULTS: Early and late asthmatic response--measured as mean maximal fall in forced expiratory volume in 1 second (FEV1) and the provocative dose of allergen that causes a 15% fall in FEV1 (PD15 allergen)--were not significantly reduced after treatment with cetirizine, compared with placebo. There was also no significant effect on the concentration of methacholine, which causes a 20% fall in FEV1 (PC20 methacholine). The increase in the level of ECP in the blood after allergen challenge was reduced after cetirizine treatment, compared with placebo, but this difference was not statistically significant. CONCLUSION: Eighteen days of treatment with cetirizine did not significantly reduce the intensity of the early and late asthmatic responses.