Respiratory symptoms and nocturnal gastroesophageal reflux: a population-based study of young adults in three European countries.

STUDY OBJECTIVE: To estimate the possible association between reported symptoms of gastroesophageal reflux (GER) after bedtime, sleep-disordered breathing, respiratory symptoms, and asthma. DESIGN: Cross-sectional international population survey. PARTICIPANTS: Participants consisted of 2,661 subjects (age range, 20 to 48 years) from three countries (Iceland, Belgium, and Sweden), of whom 2,202 were randomly selected from the general population and 459 were added because of reported asthma. MEASUREMENTS: The investigation included a structured interview, spirometry, methacholine challenge, peak flow diary, skin-prick tests, and a questionnaire on sleep disturbances. RESULTS: In the random population sample, 101 subjects (4.6%) reported GER, which was defined as the occurrence of heartburn or belching after going to bed at least once per week. Subjects with nocturnal GER more often were overweight and had symptoms of sleep-disordered breathing than participants not reporting GER. Participants with GER were more likely to report wheezing (adjusted odds ratio [OR], 2.5), breathlessness at rest (adjusted OR, 2.8), and nocturnal breathlessness (adjusted OR, 2.9), and they had increased peak flow variability compared to the subjects without GER. Physician-diagnosed current asthma was reported by 9% of subjects with GER compared to 4% of those not reporting GER (p < 0.05). Subjects with the combination of asthma and GER had a higher prevalence of nocturnal cough, morning phlegm, sleep-related symptoms, and higher peak flow variability than subjects with asthma alone. CONCLUSION: The occurrence of GER after bedtime is strongly associated with both asthma and respiratory symptoms, as well as symptoms of obstructive sleep apnea syndrome. The partial narrowing or occlusion of the upper airway during sleep, followed by an increase in intrathoracic pressure, might predispose the patient to nocturnal GER and, consequently, to respiratory symptoms.     

Effects of Obstructive Sleep Apnea and Gastroesophageal Reflux Disease on Asthma Control in Obesity

Background. Obesity is a risk factor for asthma. Obese asthmatics often have poor asthma control and respond poorly to therapy. It has been suggested that co-morbidities associated with obesity, such as reflux and obstructive sleep apnea, could be important factors contributing to poor asthma control in obese patients. Objectives. The purpose of this study was to determine if (1) reflux and/or (2) symptoms of sleep apnea contribute to poor asthma control in obesity. Methods. We studied asthmatic subjects participating in a trial of reflux treatment. Participants underwent baseline evaluation of asthma symptoms and lung function. Overall 304 participants underwent esophageal pH probe testing; 246 participants were evaluated for obstructive sleep apnea symptoms. Results. Of 402 participants in this trial, 51% were obese. Role of reflux in asthma control. Those with higher body mass index (BMI) reported a higher prevalence of reflux symptoms, but the prevalence of pH probe acid reflux was similar in all groups. Reflux was not associated with measures of asthma control in obese patients. Role of obstructive sleep apnea in asthma control. Symptoms and self-report of obstructive sleep apnea were more common with increasing BMI and associated with worse asthma control as measured by the Juniper Asthma Control questionnaire and Asthma Symptom Utility Index. Conclusions. Our data suggest that obstructive sleep apnea, but not gastroesophageal reflux disease, may contribute significantly to poor asthma control in obese patients.     

Mechanisms of nocturnal gastroesophageal reflux events in obstructive sleep apnea

Purpose  

Obstructive sleep apnea (OSA) is associated with increased nocturnal gastroesophageal reflux (nocturnal GER) events and symptoms. Treatment of OSA with continuous positive airway pressure (CPAP) reduces nocturnal GER in patients with OSA. This study sought to determine the: (1) relationship of nocturnal GER events with apnea/hypopnea and arousal, (2) effect of upper airway obstruction on the barrier function of the lower esophageal sphincter (LES), (3) mechanism of LES failure for each nocturnal GER event and (4) effect of CPAP on LES function during sleep.     

Nocturnal asthma: role of snoring and obstructive sleep apnea

In this study, we documented the clinical features of patients who had obstructive sleep apnea (OSA) and coexisting asthma and assessed the safety of nocturnal nasal continuous positive airway pressure (nCPAP) therapy on the stability of asthma. Nine patients (8 men and 1 woman) with asthma and OSA confirmed on all-night sleep study were studied. All patients suffered from frequent nocturnal asthma attacks, resulting in hospitalizations and respiratory arrests in 3. All patients had symptoms of heavy snoring, nocturnal choking, frequent sleep arousals, and excessive daytime sleepiness. They recorded their daily peak expiratory flow rates (PEFR) in the mornings and evenings, before and after bronchodilator in three 2-wk periods consisting of control, nCPAP, and control. During the period of nCPAP therapy, all patients recorded improvement in their PEFR. The mean prebronchodilator and postbronchodilator PEFR for the 9 patients were significantly higher during nCPAP therapy than during both control periods. This study confirms that nCPAP therapy can be used safely in treating patients with OSA and coexisting asthma. Furthermore, nCPAP treatment improves the asthma control and, in particular, the nocturnal attacks in this group of patients. These results also suggest that recurrent upper airway obstruction and snoring may be important triggering mechanisms of nocturnal asthma attacks.     

The impact of nocturnal symptoms associated with gastroesophageal reflux disease on health-related quality of life

BACKGROUND: Two types of reflux episodes have been identified: upright or daytime and supine or nocturnal. The population-based prevalence of symptoms of nocturnal gastroesophageal reflux disease (GERD) and the impact of those symptoms on health-related quality of life (HRQL) have not been established. METHODS: A national random-sample telephone survey was conducted to estimate the prevalence of frequent GERD and nocturnal GERD-like symptoms and to assess the relationship between HRQL, GERD, and nocturnal GERD symptoms. Respondents were classified as controls, subjects with symptomatic nonnocturnal GERD, and subjects with symptomatic nocturnal GERD. The HRQL was assessed using the Medical Outcomes Study Short-Form 36 Health Survey (SF-36). RESULTS: The prevalence of frequent GERD was 14%, with an overall prevalence of nocturnal GERD of 10%. Seventy-four percent of those with frequent GERD symptoms reported nocturnal GERD symptoms. Subjects with nonnocturnal GERD had significant decrements on the SF-36 physical and mental component summary scores compared with the US general population. Subjects reporting nocturnal GERD symptoms were significantly more impaired than subjects reporting nonnocturnal GERD symptoms on both the physical component summary (38.94 vs 41. 52; P<.001) and mental component summary (46.78 vs 49.51; P<.001) and all 8 subscales of the SF-36 (P<.001). Subjects with nocturnal GERD demonstrated considerable impairment compared with the US general population and chronic disease populations. Subjects with nocturnal GERD had significantly more pain than those with hypertension and diabetes (P<.001) and similar pain compared with those with angina and congestive heart failure. CONCLUSIONS: Nocturnal symptoms are commonly experienced by individuals who report frequent GERD symptoms. In addition, HRQL is significantly impaired in those persons who report frequent GERD symptoms, and HRQL impairment is exacerbated in those who report nocturnal GERD symptoms.     

Obstructive sleep apnea and asthma

Symptoms of sleep-disordered breathing, especially obstructive sleep apnea syndrome (OSAS), are common in asthma patients and have been associated with asthma severity. It is known that asthma symptoms tend to be more severe at night and that asthma-related deaths are most likely to occur during the night or early morning. Nocturnal symptoms occur in 60-74% of asthma patients and are markers of inadequate control of the disease. Various pathophysiological mechanisms are related to the worsening of asthma symptoms, OSAS being one of the most important factors. In patients with asthma, OSAS should be investigated whenever there is inadequate control of symptoms of nocturnal asthma despite the treatment recommended by guidelines having been administered. There is evidence in the literature that the use of continuous positive airway pressure contributes to asthma control in asthma patients with obstructive sleep apnea and uncontrolled asthma.     

Effect of nasal continuous positive airway pressure in uncontrolled nocturnal asthmatic patients with obstructive sleep apnea syndrome

The mechanisms of nocturnal asthma are intimately related to circadian rhythms, which influence inflammatory cells and mediators, hormone levels and cholinergic tone. Nocturnal airway narrowing in asthma is sometimes associated with sleep disorders, such as obstructive sleep apnea syndrome (OSAS). The aims of this study were to evaluate the association of nocturnal asthma and OSAS, and investigate the influence of continuous positive airway pressure (CPAP) therapy to improve nighttime symptoms in asthmatic patients with OSAS. Forty-three asthmatic patients who had nocturnal symptoms in spite of the optimal medical treatment according to the Global Initiative for Asthma guidelines and associated with snoring were studied. Pulmonary function tests (PFTs), asthma nighttime symptom scores, and polysomnography were performed on all patients. We treated the patients with an apnea-hypopnea index (AHI) 15 (moderate-severe OSAS) (n=16) with CPAP during 2 months. After 2 months, PFT, asthma nighttime symptom scores were reperformed. There was no significant difference in PFT values before and after CPAP treatment in OSAS patients. Asthma nighttime symptom scores were improved significantly (P<0.05) after CPAP treatment. In conclusion, in some patients with nocturnal asthma, OSAS may be responsible disease for nocturnal symptoms. In this condition, CPAP improves nocturnal symptoms without amelioration in PFT abnormalities.     

Correlation between severity of endoscopic findings and apnea-hypopnea index in patients with gastroesophageal reflux disease and obstructive sleep apnea

AIM: To assess the relationship between severity of gastroesophageal reflux disease and apnea-hypopnea index (AHI) as an indicator of the severity of obstructive sleep apnea. METHODS: Data of 57 patients with proven obstructive sleep apnea and gastroesophageal reflux disease were analyzed. Patients were divided into two groups according to severity of the sleep apnea: "mild-moderate" (A)-AHI 5≥5-30, n=27, "severe" (B)-AHI >30, n=30. All patients underwent apnea monitoring during the night, upper panendoscopy and were asked about typical reflux symptoms. RESULTS: All examined patients in both groups showed a significant overweight and there was a positive correlation between body mass index and the degree of sleep apnea (P = 0.0002). The occurence of erosive reflux disease was significantly higher in "severe" group (P = 0.0001). Using a logistic regression analysis a positive correlation was found between the endoscopic severity of reflux disease and the AHI (P = 0.016). Forty-nine point five percent of the patients experienced the typical symptoms of reflux disease at least three times a week and there was no significant difference between the two groups. CONCLUSION: A positive correlation can be found between the severity of gastroesophageal reflux disease and obstructive sleep apnea.     

Effects of 24 weeks of lansoprazole therapy on asthma symptoms, exacerbations, quality of life, and pulmonary function in adult asthmatic patients with acid reflux symptoms

BACKGROUND: Difficult-to-control asthma has been associated with gastroesophageal acid reflux. Acid-suppressive treatment has been inconsistent in improving asthma control. OBJECTIVE: To determine whether a proton-pump inhibitor improves asthma control in adult asthmatic patients with acid reflux symptoms. DESIGN: Multicenter, double-blind, randomized, placebo-controlled trial. SETTING: Twenty-nine private practices and 3 academic practices in the United States. PATIENTS: Two hundred seven patients receiving usual asthma care including an inhaled corticosteroid (ICS). Patients had acid reflux symptoms and moderate-to-severe persistent asthma. INTERVENTION: Lansoprazole, 30 mg bid, or placebo, bid, for 24 weeks. MEASUREMENTS: The primary outcome measure was daily asthma symptoms by diary. Secondary asthma outcomes included rescue albuterol use, daily morning and evening peak expiratory flow, FEV1, FVC, asthma quality of life with standardized activities (AQLQS) questionnaire score, investigator-assessed symptoms, exacerbations, and oral corticosteroid-treated exacerbations. RESULTS: Daily asthma symptoms, albuterol use, peak expiratory flow, FEV1, FVC, and investigator-assessed asthma symptoms at 24 weeks did not improve significantly with lansoprazole treatment compared to placebo. The AQLQS emotional function domain improved at 24 weeks (p = 0.025) with lansoprazole therapy. Fewer patients receiving lansoprazole (8.1% vs 20.4%, respectively; p = 0.017) had exacerbations and oral corticosteroid-treated (ie, moderate-to-severe) exacerbations (4% vs 13.9%, respectively; p = 0.016) of asthma. A post hoc subgroup analysis revealed that fewer patients receiving one or more long-term asthma-control medications in addition to an ICS experienced exacerbations (6.5% vs 24.6%, respectively; p = 0.016) and moderate-to-severe exacerbations (2.2% vs 17.5%, respectively; p = 0.021) with lansoprazole therapy. CONCLUSION: In adult patients with moderate-to-severe persistent asthma and symptoms of acid reflux, treatment with 30 mg of lansoprazole bid for 24 weeks did not improve asthma symptoms or pulmonary function, or reduce albuterol use. However, this dose significantly reduced asthma exacerbations and improved asthma quality of life, particularly in those patients receiving more than one asthma-control medication.     

Therapeutic options in the treatment of nighttime gastroesophageal reflux

Approximately three quarters of individuals who suffer from gastroesophageal reflux disease (GERD) experience its symptoms at night. Nighttime GERD symptoms disturb sleep and diminish quality of life more so than daytime symptoms. Nighttime gastroesophageal reflux is common in individuals with respiratory disorders such as sleep apnea and asthma, and may affect the severity and the frequency of these disorders. The treatments of choice for nighttime GERD symptoms are proton pump inhibitors (PPIs) due to their efficacy in relieving day- and nighttime GERD symptoms and controlling acid secretion. The onset of action, degree of acid suppression, and duration of effect of PPIs have important implications for the use of these therapies in clinical practice. PPIs that exhibit rapid and prolonged control of acid secretion may be particularly useful for treating nighttime GERD symptoms.     

阻塞性睡眠呼吸暂停低通气综合征与哮喘

最近研究表明阻塞性睡眠呼吸暂停低通气综合征(OSAHS)是支气管哮喘急性加重的独立危险因素。OSAHS常涉及睡眠时上气道吸气气流受限及气道塌陷,常与日间症状如嗜睡、抑郁、精力难以集中等相关。支气管哮喘常表现为气道慢性炎症、气道高反应、可逆性气道气流受限等。现已有大量学者对其相关性作出研究,但未达成统一共识。目前认为神经反射因素、胃食管反流、气道及全身炎症反应、睡眠结构紊乱、肥胖、心血管疾病、激素治疗及鼻部疾病等可能是OSAHS与哮喘相互影响及作用的机制。本文就OSAHS与哮喘的相关性及其机制作一综述。     

Gastroesophageal reflux in asthmatics: A double-blind, placebo-controlled crossover study with omeprazole

STUDY OBJECTIVES: To investigate the prevalence of gastroesophageal reflux (GER) among patients with asthma and to determine the effect of omeprazole on the outcome of asthma in patients with GER. DESIGN: A double-blind, placebo-controlled crossover study. SETTING: Asthmatic patients who attended the pulmonary outpatient clinic of Turku University Central Hospital, Finland. PATIENTS: One hundred seven asthmatic patients. INTERVENTIONS: The patients who were found to have GER in ambulatory esophageal pH monitoring were randomized to receive either omeprazole, 40 mg qd, or placebo for 8 weeks. After a 2-week washout period, the patients were crossed over to the other treatment. Spirometry was performed at baseline and immediately after both treatment periods. Peak expiratory values, use of sympathomimetics, and pulmonary and gastric symptoms were recorded daily in a diary. RESULTS: Pathologic GER was found in 53% of the asthmatic patients. One third of these patients had no typical reflux symptoms. Daytime pulmonary symptoms did not improve significantly (p = 0.14), but a reduction in nighttime asthma symptoms (p = 0.04) was found during omeprazole treatment. In the patients with intrinsic asthma, there was a decline in [corrected] FEV(1) values (p = 0.049). Based on symptom scores, 35% of the patients were regarded as responders to 8-week omeprazole treatment. The reflux (time [percent] of pH < 4) was found to be more severe (p = 0. 002) in the responders. CONCLUSIONS: There is a high prevalence of GER in the asthmatic population. This reflux is often clinically "silent." After an 8-week omeprazole treatment, there was a reduction in nocturnal asthma symptoms, whereas daytime asthma outcome did not improve. There seems to be a subgroup of asthma patients who benefit from excessive antireflux therapy.     

Detection of nocturnal wheezing in bronchial asthma using intermittent sleep tracheal sounds recording

Common clinical features of bronchial asthma include bronchoconstriction during the night, particularly while asleep. Although bronchoconstriction reduces the quality of life and can cause life-threatening events, a clinical technique for evaluating bronchoconstriction during sleep has not been widely applied. In this study, we measured nocturnal wheezing by intermittent sleep tracheal sounds recording (ISTSR) to detect bronchoconstriction during the hours of sleep. Using ISTSR, we studied the number and duration of nocturnal wheezing episodes in 27 adult patients with bronchial asthma. Nocturnal wheezing was detected in 36 of 39 recordings. Although the pattern of hourly nocturnal wheezing count (hourly NWC pattern) varied among subjects, there appeared to be a reproducible pattern within individuals. When wheezing alternated between long and short duration, bronchoconstriction tended to be more severe. The NWC in 1 h (NWC/H) was positively correlated with subjective symptoms and inversely correlated with the morning per cent peak expiratory flow. The hourly NWC was significantly greater at 05:00 than that at midnight. Intermittent sleep tracheal sounds recording has potential to be a non-invasive clinical tool for detecting nocturnal bronchoconstriction during hours of sleep in patients with asthma.     

Initial corticosteroid therapy for asthma

PURPOSE OF REVIEW: This review examines the commencement of maintenance pharmacotherapy for asthma: inhaled corticosteroids alone or in combination with long-acting beta2 agonists. RECENT FINDINGS: A systematic review of randomized controlled trials has examined the starting dose of inhaled corticosteroids (high, moderate, low) and the dose regimen (step down versus constant) in asthma. There was no significant difference in key asthma outcomes for step down compared with a constant inhaled corticosteroid dose. There was no significant difference between high or moderate dose inhaled corticosteroid groups (n=11) for morning peak expiratory flow, symptoms and rescue medication use. There may be a benefit from high-dose inhaled corticosteroids for airway hyperresponsiveness. There was a significant improvement in peak expiratory flow and nocturnal symptoms in favour of a moderate inhaled corticosteroid dose compared with low-dose treatment. Long-acting beta2 agonists combined with inhaled corticosteroids as initial asthma therapy has been examined in a systematic review of nine randomized controlled trials. Inhaled corticosteroids combined with long-acting beta2 agonists led to significant improvements in forced expiratory volume in 1 s, morning peak expiratory flow, symptom score and symptom-free days but no difference in exacerbations requiring oral corticosteroids. A randomized controlled trial of patients with uncontrolled asthma found a benefit of escalating doses of salmeterol/fluticasone compared with fluticasone on asthma control. SUMMARY: Initial inhaled corticosteroid therapy should begin with a constant, moderate dose. Initial therapy with long-acting beta2 agonist and inhaled corticosteroids achieves superior improvement in symptoms and lung function, and at a quicker rate than inhaled corticosteroids alone. There is no benefit in terms of reduced exacerbations unless an escalating inhaled corticosteroid dose strategy is used.     

Gastroesophageal reflux disorders and asthma

Gastroesophageal reflux (GERD) may trigger asthma. Approximately 77% of asthmatic people experience reflux symptoms, although GERD may be clinically silent in some. Esophagitis is found in 43% of asthmatic people, and 82% have abnormal esophageal acid contact times on esophageal pH testing. Clearly, GERD is prevalent in asthmatic people. Pathophysiologic mechanisms of acid-induced bronchoconstriction include a vagally mediated reflex and microaspiration. Whether these airway responses are clinically significant is the subject of some debate. Interestingly, peak expiratory flow rates and specific airway resistance alterations persist despite esophageal acid clearance. Preliminary evidence shows that substance P, an inflammatory mediator that causes airway edema, is released with esophageal acid. Although therapeutic studies are limited by their small population sizes and study design, up to 70% of asthmatic people have asthma improvement with antireflux therapy. Possible predictors of asthma response include patients with symptomatic esophageal regurgitation; abnormal proximal esophageal acid exposure; and, in surgical studies, those with normal esophageal motility and asthma response with medical therapy. Future research will further define the association between asthma and gastroesophageal reflux.     

Pulmonary aspiration shown by scintigraphy in gastroesophageal reflux-related respiratory disease

OBJECTIVES: Gastroesophageal reflux (GER) may underlie respiratory manifestations via vagally mediated airway hyperresponsiveness or microaspiration, and intraesophageal pH monitoring is generally used to identify GER in patients with such manifestations. We aimed to establish the frequency of retrograde pulmonary aspiration in patients with unexplained respiratory manifestations. METHODS: Fifty-one patients with refractory respiratory symptoms (cough, n = 18; pneumonia, n = 14; apnea, n = 8; asthma, n = 7; and laryngitis, n = 4) were prospectively evaluated. They underwent 24-h intraesophageal pH monitoring and gastroesophageal 99Tc scintigraphy with lung scan 18 to 20 h after the test meal. RESULTS: Thirteen of 51 patients (25.5%) had abnormal intraesophageal pH study results (mean reflux index, 11.3%; range, 6.5 to 50%); and in 25 of 51 patients (49%), overnight scintigraphy showed pulmonary aspiration. Nineteen of these 25 patients had entirely normal pH study results, whereas 6 of 13 patients with abnormal pH study results had aspiration. Pulmonary aspiration was demonstrated in all patients with apnea and 61.5% of patients with recurrent pneumonia. Nine of 25 patients (36%) with aspiration had histologic evidence of esophagitis, whereas histologic esophagitis was present in 5 of 13 patients (38.4%) with pathologic GER as shown by intraesophageal pH monitoring. CONCLUSIONS: Pulmonary aspiration as demonstrated by overnight scintigraphy is common in children with unexplained and refractory respiratory manifestations, suggesting that GER could be the underlying cause of these manifestations. Since only a few children with chronic or recurrent respiratory symptoms have a pathologic gastroesophageal acid reflux, a normal intraesophageal pH study result does not rule out GER in these children.     

Obstructive sleep apnea in infants

Obstructive sleep apnea in infants has a distinctive pathophysiology, natural history, and treatment compared with that of older children and adults. Infants have both anatomical and physiological predispositions toward airway obstruction and gas exchange abnormalities; including a superiorly placed larynx, increased chest wall compliance, ventilation-perfusion mismatching, and ventilatory control instability. Congenital abnormalities of the airway, such as laryngomalacia, hemangiomas, pyriform aperture stenosis, choanal atresia, and laryngeal webs, may also have adverse effects on airway patency. Additional exacerbating factors predisposing infants toward airway collapse include neck flexion, airway secretions, gastroesophageal reflux, and sleep deprivation. Obstructive sleep apnea in infants has been associated with failure to thrive, behavioral deficits, and sudden infant death. The proper interpretation of infant polysomnography requires an understanding of normative data related to gestation and postconceptual age for apnea, arousal, and oxygenation. Direct visualization of the upper airway is an important diagnostic modality in infants with obstructive apnea. Treatment options for infant obstructive sleep apnea are predicated on the underlying etiology, including supraglottoplasty for severe laryngomalacia, mandibular distraction for micrognathia, tonsillectomy and/or adenoidectomy, choanal atresia repair, and/or treatment of gastroesophageal reflux.     

Gastro-oesophageal reflux and nocturnal asthma

Gastro-oesophageal (GO) reflux is believed to be a possible cause of nocturnal asthma. The aim of this study was to see if there is any correlation between the incidence of GO-reflux at night and nocturnal asthma. Thirty-seven adult patients with a history of nocturnal asthma for more than one hundred days a year and of reflux disease were evaluated using 24 h pH-monitoring of the oesophagus and measurement of peak expiratory flow (PEF) rate every hour when awake. Half of the patients suffered from severe GO-reflux at night, whilst the other half had no nocturnal reflux. Respiratory symptoms and inhalation of beta-2 agonists were recorded during the night and PEF was recorded when the patients awoke in the morning. A significant correlation was found between reflux at night and the degree of bronchial obstruction in the early morning, but not between night-time reflux and nocturnal respiratory symptoms. It would appear that GO-reflux in most asthmatics is neither a strong nor immediate trigger factor in nocturnal asthma, although it does seem to influence bronchial obstruction during the night as was demonstrated by a low morning-PEF value.     

Impact of CPAP on asthmatic patients with obstructive sleep apnoea.

The impact of continuous positive airway pressure (CPAP) treatment on the airway responsiveness of asthmatic subjects with obstructive sleep apnoea (OSA) has scarcely been studied. A prospective study was performed comparing the changes in airway responsiveness and quality of life in stable asthmatic OSA patients, before and 6 weeks after their nocturnal CPAP treatment. A total of 20 subjects (11 males and nine females) participated in the study. With the nocturnal CPAP treatment, the apnoea/hypopnoea index dropped from 48.1 +/- 23.6 x h(-1) to 2.6 +/- 2.5 x h(-1). There were no significant changes in airway responsiveness after CPAP treatment (provocative concentration causing a 20% fall in forced expiratory volume in one second (FEV(1); PC(20) 2.5 mg x mL(-1) (1.4-4.5)) compared with baseline (PC(20) 2.2 mg x mL(-1) (1.3-3.5)). There was no significant change in FEV(1) either. However, the asthma quality of life of the subjects improved from 5.0 +/- 1.2 at baseline to 5.8 +/- 0.9 at the end of the study. In conclusion, nocturnal continuous positive airway pressure treatment did not alter airway responsiveness or forced expiratory volume in one second in subjects with stable mild-to-moderate asthma and newly diagnosed obstructive sleep apnoea. However, nocturnal continuous positive airway pressure treatment did improve asthma quality of life.     

Salmeterol vs theophylline: sleep and efficacy outcomes in patients with nocturnal asthma.

STUDY OBJECTIVES: To compare the efficacy, safety, and effects on sleep quality of salmeterol and extended-release theophylline in patients with nocturnal asthma. DESIGN: Randomized, double-blind, double-dummy, three-period crossover. SETTING: Outpatients at a single center. Patients spent 1 night during screening and 2 nights during each study period in a sleep laboratory for completion of sleep studies. PATIENTS: Male and female patients who were at least 18 years old with nocturnal asthma (baseline FEV1, 50 to 90% of predicted) and who required regular bronchodilator therapy. Patients on inhaled corticosteroids, cromolyn, and nedocromil were allowed into the study if their dosing remained constant throughout the study. INTERVENTIONS: Inhaled salmeterol (42 microg per actuation), extended-release oral theophylline (titrated to serum levels of 10 to 20 microg/mL), and placebo taken twice daily. MEASUREMENTS AND RESULTS: Efficacy measurements included nocturnal spirometry, nocturnal polysomnography, sleep questionnaires, and daily measurements of lung function and symptoms. Salmeterol was superior to theophylline (p < or = 0.05) in maintaining nocturnal FEV1 levels and was superior to placebo (p < or = 0.05) in improving morning and evening peak expiratory flow (PEF) and in decreasing nighttime albuterol use. The use of salmeterol significantly increased the percentage of days and nights with no albuterol use and decreased daytime albuterol use compared with theophylline and placebo (p < or = 0.05). Sleep quality global scores significantly improved with salmeterol and placebo (p < 0.001) but not with theophylline. The effects on sleep architecture were similar across treatment groups. CONCLUSIONS: Salmeterol (but not theophylline) was associated with sustained improvements in morning PEF, protection from nighttime lung function deterioration, reductions in albuterol use, and improvements in patient perceptions of sleep. No differences were seen in polysomnographic measures of sleep quality.