Hannu Tukiainen

Lifestyle intervention with weight reduction: first-line treatment in mild obstructive sleep apnea

RATIONALE Obesity is the most important risk factor for obstructive sleep apnea (OSA). However, although included in clinical guidelines, no randomized controlled studies have been performed on the effects of weight reduction on mild OSA. OBJECTIVES The aim of this prospective, randomized controlled parallel-group 1-year follow-up study was to determine whether a very low calorie diet (VLCD) with supervised lifestyle counseling could be an effective treatment for adults with mild OSA. METHODS Seventy-two consecutive overweight patients (body mass index, 28-40) with mild OSA were recruited. The intervention group (n = 35) completed the VLCD program with supervised lifestyle modification, and the control group (n = 37) received routine lifestyle counseling. The apnea-hypopnea index (AHI) was the main objectively measured outcome variable. Change in symptoms and the 15D-Quality of Life tool were used as subjective measurements. MEASUREMENTS AND MAIN RESULTS The lifestyle intervention was found to effectively reduce body weight (-10.7 +/- 6.5 kg; body mass index, -3.5 +/- 2.1 [mean +/- SD]). There was a statistically significant difference in the mean change in AHI between the study groups (P = 0.017). The adjusted odds ratio for having mild OSA was markedly lowered (odds ratio, 0.24 [95% confidence interval, 0.08-0.72]; P = 0.011) in the intervention group. All common symptoms related to OSA, and some features of 15D-Quality of Life improved after the lifestyle intervention. Changes in AHI were strongly associated with changes in weight and waist circumference. CONCLUSIONS VLCD combined with active lifestyle counseling resulting in marked weight reduction is a feasible and effective treatment for the majority of patients with mild OSA, and the achieved beneficial outcomes are maintained at 1-year follow-up.

Sustained improvement in mild obstructive sleep apnea after a diet- and physical activity-based lifestyle intervention: postinterventional follow-up.

BACKGROUND Obesity is the most important risk factor for obstructive sleep apnea (OSA). Weight-reduction programs have been observed to represent effective treatment of overweight patients with OSA. However, it is not known whether beneficial changes remain after the end of the intervention. OBJECTIVE The aim of the study was to assess the long-term efficacy of a lifestyle intervention based on a healthy diet and physical activity in a randomized, controlled, 2-y postintervention follow-up in OSA patients. DESIGN Eighty-one consecutive overweight [body mass index (in kg/m(2)): 28-40] adult patients with mild OSA were recruited. The intervention group completed a 1-y lifestyle modification regimen that included an early 12-wk weight-reduction program with a very-low-calorie diet. The control group received routine lifestyle counseling. During the second year, no dietary counseling was offered. Change in the apnea-hypopnea index (AHI) was the main objective outcome variable, and changes in symptoms were used as a subjective measurement. RESULTS A total of 71 patients completed the 2-y follow-up. The mean (± SD) changes in diet and lifestyle with simultaneous weight reduction (-7.3 ± 6.5 kg) in the intervention group reflected sustained improvements in findings and symptoms of OSA. After 2 y, the reduction in the AHI was significantly greater in the intervention group (P = 0.049). The intervention lowered the risk of OSA at follow-up; the adjusted odds ratio for OSA was 0.35 (95% CI: 0.12-0.97; P = 0.045). CONCLUSION Favorable changes achieved by a 1-y lifestyle intervention aimed at weight reduction with a healthy diet and physical activity were sustained in overweight patients with mild OSA after the termination of supervised lifestyle counseling. This trial was registered at clinicaltrials.gov as NCT00486746.

Effect of weight reduction on rhinometric measurements in overweight patients with obstructive sleep apnea

Background Elevated nasal resistance and obesity predispose to obstructive sleep apnea (OSA). Weight loss has been shown to result in an alleviation of OSA, but its effect on nasal airflow has not been studied. Methods This study was a prospective, randomized, controlled study with two parallel groups. A total of 52 adult overweight patients (body mass index [BMI], 28–40 kg/m2) with mild obstructive sleep apnea (apnea–hypopnea index {AHI}, 5–15) were randomized into two study groups. The intervention group (n = 26) followed a very low calorie diet with a supervised lifestyle intervention while the control group (n = 26) received routine lifestyle counseling. The changes in BMI, total nasal resistance, total nasal volume, and quality of life scores (Mini Rhinoconjunctivitis Quality of Life Questionnaire, MiniRQLQ) were assessed at baseline and after the intervention at 3 months. Results The reduction in BMI in the intervention group was significantly greater than that achieved by patients in the control group (5.4 kg/m2 versus 0.5 kg/m2). Accordingly, AHI was reduced by 3.2 events/hour in the intervention group and by 1.3 in the control group. However, there were no significant changes in rhinometric measurements despite significant weight loss. There was no correlation between the reduction of BMI and the change in nasal resistance or MiniRQLQ scores. Conclusion Weight reduction does not seem to have any effect on nasal resistance or volume in overweight patients with mild OSA. Patients with OSA and impaired nasal breathing need specific medical or surgical treatment to restore nasal airflow.

Pulmonary Deposition and Clinical Response of99mTc-Labelled Salbutamol Delivered from a Novel Multiple Dose Powder Inhaler

Pulmonary deposition of 99mTc-labelled sulbutamol was determined after delivery from a novel multiple dose powder inhaler (Easyhaler®). The clinical efficacy of the inhalation powder, evaluated simultaneously with gamma camera detection, was compared with that obtained after drug delivery from a metered dose inhaler-spacer combination. The study was performed as an open, non-randomized cross-over trial. A single dose of radiolabelled inhalation powder was inhaled on the first and the inhalation aerosol, as control, on the second study day. Sulbutamol sulphate was labelled with 99mtechnetium, and the inhalation powder was formulated by mixing radioactive drug particles with carrier material. Aerodynamic properties of the radiolabelled inhalation powder were similar to those of the unlabelled salbutamol powder. Delivered dose from the breath-actuated powder inhaler was adjusted to be equal to two puffs from a conventional aerosol actuator with a short plastic mouthpiece. Twelve non-smoking asthmatic patients participated in the trial. The mean pulmonary deposition of 24% was obtained after drug delivery from Easyhaler® powder inhaler. Clinical efficacy of the medications was similar in terms of area under the FEV1 curve, maximum FEV1 and the improvement ratio. Thus it can be suggested that powder delivery from Easyhaler® powder inhaler and the aerosol delivery through the spacer are equally effective.

Occupational and Environmental Lung DiseaseInhalation Challenge With Bovine Dander Allergens: Who Needs It?

STUDY OBJECTIVES To identify which tests would be useful in selecting patients for a specific inhalation challenge with bovine dander allergens (bSIC). DESIGN A prospective study. SETTING A university hospital. PATIENTS Thirty-seven dairy farmers with a clinical suspicion of occupational asthma due to bovine allergens. INTERVENTIONS Each patient (n = 27) underwent histamine challenge, mannitol challenge, exhaled nitric oxide (NO) measurement, bovine-specific serum IgE measurement, and skin-prick test (SPT) with bovine allergens prior to undergoing a bSIC. RESULTS Eleven patients responded to the inhalation challenge with bovine allergens. The sensitivity and specificity of the tests, based on this response, were 82% and 65%, respectively, for the histamine challenge; 20% and 94%, respectively, for the mannitol challenge; 27% and 77%, respectively, for the NO measurement; 82% and 100%, respectively, for the bovine-specific serum IgE measurement; and 100% and 50%, respectively, for the SPT. Multiple regression analysis revealed that only IgE-mediated sensitivity to bovine allergens, but neither bronchial hyperreactivity nor exhaled NO concentration, contributed significantly to the response. CONCLUSION Only the SPT with bovine allergens and bovine-specific serum IgE measurements were useful in selecting patients for the bSIC. This challenge should not be performed in SPT-negative subjects. A diagnosis of occupational asthma due to bovine dander allergens could be made without an inhalation challenge test in asthmatic patients with high bovine-specific serum IgE levels. This practice would eliminate the need for the majority of bSICs.

Effect of Cold Air on Exercise Capacity in COPD : Increase or Decrease?

STUDY OBJECTIVE To clarify the effect of cold air on exercise capacity in COPD. DESIGN Cycle ergometer tests under different environmental conditions. SETTING Pulmonary function laboratory and an environmental chamber at a university hospital. PARTICIPANTS Eighteen patients with stable COPD; 14 completed the study. INTERVENTIONS A preliminary cycle ergometer test followed by two incremental, symptom-limited cycle ergometer tests, one at 24 degrees C and the other at -20 degrees C. MEASUREMENTS On the first study day: arterial blood gas analysis, 12 to 15 s maximal voluntary ventilation, maximal expiratory flow-volume curves before and 1 h after inhalation of 80 microg of ipratropium bromide, and diffusion capacity of the lung. During the exercise challenges: spirometric indices, minute ventilation (VE), oxygen consumption (VO2), carbon dioxide production (VCO2), facial skin temperature, and heart rate. The feeling of dyspnea was assessed with a visual analogue scale. RESULTS The maximal work load was 87.5+/-7.3 W at -20 degrees C compared with 96.4+/-6.9 W at 24 degrees C (p<0.05). Accordingly, the exercise duration was shorter in the cold. Exercise dyspnea was more severe in the cold at equal work loads. The shortening of exercise duration induced by cold air correlated with the enhancement of exercise dyspnea. Furthermore, cold air cooled the facial skin and induced immediate bronchoconstriction. VE, VO2, VCO2, and heart rate did not differ between the warm and cold challenges. CONCLUSIONS Cold air decreases exercise capacity in COPD, probably by increasing exercise dyspnea.

Effect of weight loss on inflammation in patients with mild obstructive sleep apnea

BACKGROUND AND AIMS Inflammation may be one mediating mechanism for cardiovascular diseases in obstructive sleep apnea (OSA). However, little is known about subclinical inflammation or the effect of lifestyle intervention on inflammation in early stages of OSA. The aim of this substudy of an existing randomized controlled trial, with post hoc analyses, was to determine the impact of lifestyle changes aimed at weight reduction on inflammatory biomarkers in overweight patients with mild OSA. METHODS AND RESULTS Patients were randomized to supervised intensive lifestyle intervention group (N=28) or to control group (N=31), which received routine lifestyle advices. Circulating concentrations of pro- and anti-inflammatory mediators were measured before and after the 1-year intervention. The concentrations of two pro-inflammatory mediators, high-sensitivity C-reactive protein (hsCRP) and interleukin (IL)-6, decreased significantly in both groups. Although the changes in inflammatory biomarkers favored the supervised lifestyle intervention, the only significant reduction observed between the groups was for the anti-inflammatory IL-1 receptor antagonist (IL-1RA). The change in hsCRP was associated with apnea-hypopnea index, and improving night-time oxygen saturation was related to tumor necrosis factor alpha. IL-1RA and IL-6 were associated with insulin metabolism. CONCLUSION Weight loss resulted in reductions in concentrations of some pro- and anti-inflammatory mediators in overweight patients with mild OSA, overall favoring the supervised lifestyle intervention. These findings suggest that more intensive treatment of obesity in OSA patients might be well-justified.

Clinical Investigations: AsthmaEffect of Cold Air on Exercise Capacity in COPD: Increase or Decrease?

STUDY OBJECTIVE To clarify the effect of cold air on exercise capacity in COPD. DESIGN Cycle ergometer tests under different environmental conditions. SETTING Pulmonary function laboratory and an environmental chamber at a university hospital. PARTICIPANTS Eighteen patients with stable COPD; 14 completed the study. INTERVENTIONS A preliminary cycle ergometer test followed by two incremental, symptom-limited cycle ergometer tests, one at 24 degrees C and the other at -20 degrees C. MEASUREMENTS On the first study day: arterial blood gas analysis, 12 to 15 s maximal voluntary ventilation, maximal expiratory flow-volume curves before and 1 h after inhalation of 80 microg of ipratropium bromide, and diffusion capacity of the lung. During the exercise challenges: spirometric indices, minute ventilation (VE), oxygen consumption (VO2), carbon dioxide production (VCO2), facial skin temperature, and heart rate. The feeling of dyspnea was assessed with a visual analogue scale. RESULTS The maximal work load was 87.5+/-7.3 W at -20 degrees C compared with 96.4+/-6.9 W at 24 degrees C (p<0.05). Accordingly, the exercise duration was shorter in the cold. Exercise dyspnea was more severe in the cold at equal work loads. The shortening of exercise duration induced by cold air correlated with the enhancement of exercise dyspnea. Furthermore, cold air cooled the facial skin and induced immediate bronchoconstriction. VE, VO2, VCO2, and heart rate did not differ between the warm and cold challenges. CONCLUSIONS Cold air decreases exercise capacity in COPD, probably by increasing exercise dyspnea.