Clinical trial NCT01383564: Continuous Positive Airway Pressure Use in Asthma With Moderate to Severe Obstructive Sleep Apnea Patients
Official title: Effect of Nasal Continuous Positive Airway Pressure in Uncontrolled Nocturnal Asthmatic Patients With Moderate Obstructive Sleep Apnea Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: OSA
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2011-06-28
Enrollment: 101
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Obstructive sleep apnea syndrome (OSAS) and asthma are both common disorders in Hong Kong, with prevalence of at least 4% among the middle-aged male Hong Kong (HK) Chinese populations and 7.2% in young adults respectively. OSAS is characterized by repetitive episodes of upper airway obstruction, causing intermittent hypoxia, sleep fragmentation, disabling daytime sleepiness, impaired cognitive function and poor health status. Continuous positive airway pressure (CPAP) is the first line of therapy for sleep apnea. CPAP provides a pneumatic stent for the upper airway, eliminating the airway collapse during inspiration.

Asthma is a chronic inflammatory disorder of airways, characterized by airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathless, chest tightness, and coughing, particularly at night or in the early morning. Nocturnal asthma is not a different condition from asthma and is defined as a variable worsening of asthma at night, in which the mechanisms are not completely understood.

The prevalence of OSAS in asthmatic patients has not yet been studied, but several studies have reported an increased prevalence of OSAS symptoms in asthmatic patients. OSAS and asthma share some common risk factors, which include obesity, gastroesophageal reflux and rhinitis. CPAP treatment has been shown in prospective clinical studies to have a positive impact on asthma outcome in patients with concomitant OSAS, for example, improvement of asthma related quality of life in subjects with stable mild-to-moderate asthma, but there was no change in the airway responsiveness or forced expiratory volume in one second. Although important, these studies included small numbers of participants used nonrandomized designs. This study is to assess the impact of CPAP treatment on asthma control among patients with nocturnal symptoms and moderate OSAS.

Detailed description: Obstructive sleep apnea syndrome (OSAS) and asthma are both common disorders in Hong Kong, with prevalence of at least 4% among the middle-aged male Hong Kong (HK) Chinese populations and 7.2% in young adults respectively. OSAS is characterized by repetitive episodes of upper airway obstruction, causing intermittent hypoxia, sleep fragmentation, disabling daytime sleepiness, impaired cognitive function and poor health status. Continuous positive airway pressure (CPAP) is the first line of therapy for sleep apnea. CPAP provides a pneumatic stent for the upper airway, eliminating the airway collapse during inspiration.

Asthma is a chronic inflammatory disorder of airways, characterized by airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathless, chest tightness, and coughing, particularly at night or in the early morning. Nocturnal asthma is not a different condition from asthma and is defined as a variable worsening of asthma at night, in which the mechanisms are not completely understood. It may be driven by circadian rhythms of circulating hormones such as epinephrine, cortisol, and melatonin and neural mechanisms such as cholinergic tone. An increase in airway inflammation at night has been reported. This might reflect a reduction in endogenous anti-inflammatory mechanisms. Other factors that have been proposed as possible causes for overnight bronchoconstriction are interruption of bronchodilator or other treatment, allergens in bedding, airway cooling, supine posture, and gastroesophageal reflux (GER).

Prevalence of OSAS in asthma: The prevalence of OSAS in asthmatic patients has not yet been studied, but several studies have reported an increased prevalence of OSAS symptoms in asthmatic patients. Large epidemiologic studies demonstrated that asthma patients are more frequently report snoring. In a longitudinal study, asthma was an independent risk factor for development of snoring. OSAS symptoms are highly prevalent in clinic-based populations of well-characterized asthma patients. Polysomnography revealed high frequencies of OSAS (88% and 95.5%) in patients with difficult-to-control asthma.

Common risk factors contributing OSAS asthma: OSAS and asthma share some common risk factors. Fifty percent of the obese in Caucasian populations have OSAS, and among those with OSAS, 40% are obese. However, in a community study of sleep-disordered breathing in middle-aged Chinese men in Hong Kong, the average body mass index (BMI) of habitual snorer was 25.1 kg/m2 and that of OSAS was 27kg/m2, making the contribution of obesity in OSAS less as important as in the western counterpart. Apart from obesity, the prevalence of GER is increased in patients with OSAS. It has been suggested that obesity contributes to the same risk factors for OSAS and GER. However, OSAS patients exhibit significantly more GER than do members of the average population even when one controls for alcohol intake and BMI. GER occurring during sleep is a well-known trigger for nocturnal asthma and can provoke asthma symptoms through vagal reflexes induced by exposure of the esophagus to acid. OSAS-induced acid reflux may play a causative role in triggering asthma symptoms. Another possible etiology for the high prevalence of OSAS symptoms in asthmatic patients is the increased incidence of nasal obstruction in asthmatic patients. The nose is preferred breathing route during sleep, and nasal obstruction contributes to sleep disordered breathing in predisposed individuals. Rhinitis and chronic sinusitis are common conditions that may cause nasal congestion and consequently contribute to upper airway obstruction in OSAS.

The effect of CPAP treatment on asthma control:

CPAP treatment has been shown in prospective clinical studies to have a positive impact on asthma outcome in patients with concomitant OSAS. Although important, these studies included small numbers of participants used nonrandomized designs.

We hypothesize that OSAS contribute to the symptoms related to nocturnal asthma and that CPAP therapy would improve the asthma symptoms, airway hyperactivity and quality of life in patients with nocturnal asthma and OSAS. We aim to assess (1) asthma control, airway responsiveness, daytime sleepiness, cognitive function and health status at baseline and at 3 months after nasal CPAP treatment among our asthma patients with nocturnal symptoms and OSAS; (2) the acceptance and compliance of nasal CPAP treatment.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* at least one nocturnal awakening or early morning awakening caused by asthmatic symptoms (cough, wheeze, chest tightness, and breathlessness)
* habitual snoring; able to give consent for joining the study

Exclusion Criteria:

* active smoking or quit smoking \<6 months or smoking history \>10 pack-years
* Cardiac failure
* cerebrovascular disease
* lung disease except asthma
* dementia or poor hand function that would inhibit the patients cooperating the sleep study or CPAP treatment

Primary outcomes:
measure: Asthma control test score
timeFrame: 3 months
Secondary outcomes:
measure: Spirometry
timeFrame: 3 months
measure: Epworth Sleepiness Score (ESS)
timeFrame: 3 months
measure: SF 36 questionnaire
timeFrame: 3 months
measure: Bronchial challenge test
timeFrame: 3 months
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: Prince of Wales Hospital
state: Hong Kong
Study officials:
affiliation: Chinese Univesrity of Hong Kong
name: Susanna SS Ng, MBChB
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ng SSS, Chan TO, To KW, Chan KKP, Ngai J, Yip WH, Lo RLP, Ko FWS, Hui DSC. Continuous positive airway pressure for obstructive sleep apnoea does not improve asthma control. Respirology. 2018 Nov;23(11):1055-1062. doi: 10.1111/resp.13363. Epub 2018 Jul 10.