Exertional breathlessness related to medical conditions in middle-aged people: the population-based SCAPIS study of more than 25,000 men and women.

BACKGROUND: Breathlessness is common in the population and can be related to a range of medical conditions. We aimed to evaluate the burden of breathlessness related to different medical conditions in a middle-aged population. METHODS: Cross-sectional analysis of the population-based Swedish CArdioPulmonary bioImage Study of adults aged 50-64 years. Breathlessness (modified Medical Research Council [mMRC] ≥ 2) was evaluated in relation to self-reported symptoms, stress, depression; physician-diagnosed conditions; measured body mass index (BMI), spirometry, venous haemoglobin concentration, coronary artery calcification and stenosis [computer tomography (CT) angiography], and pulmonary emphysema (high-resolution CT). For each condition, the prevalence and breathlessness population attributable fraction (PAF) were calculated, overall and by sex, smoking history, and presence/absence of self-reported cardiorespiratory disease. RESULTS: We included 25,948 people aged 57.5 ± [SD] 4.4; 51% women; 37% former and 12% current smokers; 43% overweight (BMI 25.0-29.9), 21% obese (BMI ≥ 30); 25% with respiratory disease, 14% depression, 9% cardiac disease, and 3% anemia. Breathlessness was present in 3.7%. Medical conditions most strongly related to the breathlessness prevalence were (PAF 95%CI): overweight and obesity (59.6-66.0%), stress (31.6-76.8%), respiratory disease (20.1-37.1%), depression (17.1-26.6%), cardiac disease (6.3-12.7%), anemia (0.8-3.3%), and peripheral arterial disease (0.3-0.8%). Stress was the main factor in women and current smokers. CONCLUSION: Breathlessness mainly relates to overweight/obesity and stress and to a lesser extent to comorbidities like respiratory, depressive, and cardiac disorders among middle-aged people in a high-income setting-supporting the importance of lifestyle interventions to reduce the burden of breathlessness in the population.

Nocturnal gastro-oesophageal reflux and respiratory symptoms are increased in sleep apnoea: comparison with the general population.

AIM: To assess respiratory symptoms and nocturnal gastro-oesophageal reflux (nGER) among untreated obstructive sleep apnoea (OSA) patients, compared with the general population. Also, if nGER associates differently with respiratory symptoms among OSA patients. METHODS: 2 study cohorts were included: 822 newly diagnosed subjects with moderate-severe OSA and 738 Icelandic general population study participants. All participants answered the same questionnaires. Those reporting nGER symptoms at least once per week were defined as 'with nGER'; those without nGER symptoms and without nGER medication were defined as 'no nGER'; and other participants were defined as having 'possible nGER'. Propensity score-based weights were used to minimise confounding and selection bias and facilitate causal interpretations. RESULTS: The prevalence of nGER among OSA patients was 14.1%, compared with 5.8% in the general population. This increased prevalence in OSA was not explained by differences in age, gender, body mass index, smoking, hypertension and diabetes (adjusted OR (95% CI)=3.79 (2.24 to 6.43)). OSA patients 'with nGER' and with 'possible nGER' reported more wheezing (44% and 44% vs 25%, respectively) and productive cough (47% and 42% vs 29%, respectively), compared with OSA patients with 'no nGER'. The same pattern was seen in the general population, although with a generally lower prevalence. The effect of nGER on respiratory symptoms was similar between the two cohorts. CONCLUSION: nGER was more often reported among untreated moderate-severe OSA patients than in the general population. Participants with nGER had more wheezing and productive cough, both among untreated OSA patients and in the general population.

Gastroesophageal reflux and snoring are related to asthma and respiratory symptoms: Results from a Nordic longitudinal population survey.

AIM: To study if individuals with nocturnal gastroesophageal reflux (nGER) and habitual snoring are more likely to develop asthma and respiratory symptoms (i.e. wheeze, cough, chest tightness, breathlessness) than those without these conditions, and if these associations are additive. METHODS: We used data from the population-based prospective questionnaire study Respiratory Health in Northern Europe (RHINE) (11,024 participants), with data from 1999 and 2011. Participants with heartburn or belching after going to bed, at least 1 night/week, were considered to have nGER. Participants reporting loud snoring at least 3 nights/week were considered to have habitual snoring. Participants were grouped into four groups by their nGER and snoring status: "never"; "former"; "incident"; "persistent". Incident respiratory symptoms were analyzed among participants without respective symptom at baseline. RESULTS: Snoring and nGER were independently associated with incident asthma and respiratory symptoms. The risk of incident wheeze was increased in subjects with incident or persistent snoring (adjusted odds ratio (95 % CI): 1.44 (1.21-1.72)), nGER (2.18 (1.60-2.98)) and in those with both snoring and nGER (2.59 (1.83-3.65)). The risk of developing asthma was increased in subjects with incident or persistent snoring (1.44 (1.15-1.82)), nGER (1.99 (1.35-2.93)) and in those with both snoring and nGER (1.72 (1.06-2.77)). No significant interaction was found between snoring and nGER. A similar pattern was found for the incidence of all other respiratory symptoms studied, with the highest risk among those with both incident or persistent nGER and snoring. CONCLUSION: The risk of developing asthma and respiratory symptoms is increased among subjects with nGER and habitual snoring. These associations are independent of each other and confounding factors. Snoring and nGER together are additive on respiratory symptoms.

Positive airway pressure treatment affects respiratory symptoms and gastro-oesophageal reflux: the Icelandic Sleep Apnea Cohort Study.

Aim: To study the effect of positive airway pressure (PAP) treatment on nocturnal gastro-oesophageal reflux (nGOR) and respiratory symptoms among clinical obstructive sleep apnoea (OSA) patients. Methods: 822 patients newly diagnosed with OSA referred for PAP treatment were recruited. 732 patients had a 2-year follow-up visit with continuous PAP compliance data (366 full PAP users, 366 partial/non-PAP users). They answered questionnaires, including reporting of nGOR, sleep and respiratory symptoms and general health. Patients with nGOR symptoms once a week or more were defined as "with nGOR". Those without nGOR symptoms and nGOR medication were defined as "no nGOR". Others were defined as "possible nGOR". Results: At 2-year follow-up, PAP treatment among full users resulted in decreased nGOR (adjusted OR 0.58, 95% CI 0.40-0.86) and wheezing (adjusted OR 0.56, 95% CI 0.35-0.88) compared with partial/non-PAP users. Decreased nGOR, among both full and partial/non-users of PAP treatment, was associated with a decrease in productive morning cough (adjusted OR 4.70, 95% CI 2.22-9.99) and a decrease in chronic bronchitis (adjusted OR 3.86, 95% CI 1.74-8.58), but not decreased wheezing (adjusted OR 0.90, 95% CI 0.39-2.08). A mediation analysis found that PAP treatment directly led to a decrease in wheezing, not mediated through nGOR. Conversely, PAP treatment decreased productive cough mediated through a decrease in nGOR. Conclusion: In an unselected group of OSA patients, PAP treatment for 2 years was associated with a decrease in nGOR and respiratory symptoms. The PAP treatment itself was associated with less wheezing. A decrease in nGOR through PAP treatment was associated with a decrease in productive cough.

High prevalence of interstitial lung abnormalities in middle-aged never-smokers.

Background: Interstitial lung abnormalities (ILA) are incidental findings on chest computed tomography (CT). These patterns can present at an early stage of fibrotic lung disease. Our aim was to estimate the prevalence of ILA in the Swedish population, in particular in never-smokers, and find out its association with demographics, comorbidities and symptoms. Methods: Participants were recruited to the Swedish CArdioPulmonary BioImage Study (SCAPIS), a population-based survey including men and women aged 50-64 years performed at six university hospitals in Sweden. CT scan, spirometry and questionnaires were performed. ILA were defined as cysts, ground-glass opacities, reticular abnormality, bronchiectasis and honeycombing. Findings: Out of 29 521 participants, 14 487 were never-smokers and 14 380 were men. In the whole population, 2870 (9.7%) had ILA of which 134 (0.5%) were fibrotic. In never-smokers, the prevalence was 7.9% of which 0.3% were fibrotic. In the whole population, age, smoking history, chronic bronchitis, cancer, coronary artery calcium score and high-sensitive C-reactive protein were associated with ILA. Both ILA and fibrotic ILA were associated with restrictive spirometric pattern and impaired diffusing capacity of the lung for carbon monoxide. However, individuals with ILA did not report more symptoms compared with individuals without ILA. Interpretation: ILA are common in a middle-aged Swedish population including never-smokers. ILA may be at risk of being underdiagnosed among never-smokers since they are not a target for screening.

Risk and outcomes of COVID-19 in patients with oxygen-dependent chronic respiratory failure- a national cohort study.

BACKGROUND: We aimed to evaluate cumulative occurrence and impact of COVID-19 in patients with chronic respiratory failure (CRF) treated with long-term oxygen therapy (LTOT). MATERIAL AND METHODS: Data were obtained from the SCIFI-PEARL study on the entire Swedish population and on patients with oxygen-dependent CRF and no COVID-19 diagnosis before start of LTOT. Analyses were performed for three time periods; pre-alpha (Jan-Dec 2020), alpha (Jan-Mar 2021) and delta/omicron (Apr 2021-May 2022). Cumulative incidence of laboratory-verified COVID-19 was compared between patients with CRF and the general population. Risk factors for severe (hospitalised) to critical (intensive care, or death ≤30 days after infection) COVID-19, and the impact of COVID-19 on one-year mortality, were analysed using multivariable Cox regression. RESULTS: Cumulative incidence of COVID-19 was higher in patients with CRF than in the general population during the pre-alpha period (6.4%/4.9%, p = 0.002), but less common during the alpha and delta/omicron periods (2.9%/3.8% and 7.8%/15.5%, p < 0.0001 for both). The risk of severe/critical COVID-19 was much higher in CRF patients during all periods (4.9%/0.5%, 3.8%/0.2% and 15.5%/0.5%, p < 0.0001 for all). Risk factors for COVID-19 infection in people with CRF were higher age, cardiovascular and renal disease, and COVID-19 was associated with increased one-year mortality following infection in the pre-alpha (HR 1.79; [95% CI] 1.27-2.53) and alpha periods (1.43; 1.03-1.99). CONCLUSION: Patients with CRF had higher risk of severe/critical COVID-19 than the general population. COVID-19 infection was associated with excess one-year mortality.

Exhaled biomarkers in adults with non-productive cough.

BACKGROUND: Chronic cough is a common condition but disease mechanisms are not fully understood. Our aim was to study respiratory biomarkers from the small airways in individuals with non-productive cough. METHODS: A cohort of 107 participants answered detailed questionnaires, performed spirometry, exhaled NO measurement, impulse oscillometry, gave blood samples and particles in exhaled air (PEx) samples. Current smokers (N = 38) were excluded. A total of 14 participants reported non-productive cough (cases). A total of 55 participants reported no cough (control group). PEx samples, containing exhaled particles derived from small airways, were collected and analysed with the SOMAscan proteomics platform. RESULTS: Participants with non-productive cough had similar age, sex, BMI, and inflammation markers in blood tests, as participants without cough. The proteomics analysis found 75 proteins significantly altered among participants with chronic cough compared to controls, after adjusting for sex and investigator performing the PExA measurement (all with p-value < 0.05 and q-value ≤ 0.13, thereof 21 proteins with a q-value < 0.05). These proteins were mostly involved in immune and inflammatory responses, complement and coagulation system, but also tight junction proteins and proteins involved in neuroinflammatory responses. CONCLUSIONS: This exploratory study on proteomics of exhaled particles among individuals with chronic cough found alterations in relative abundance of 75 proteins. The proteins identified are implicated in both pathways known to be implicated in cough, but also potentially new pathways. Further studies are needed to explore the importance of these findings.

Different chest HRCT scan protocols change the extent of ground glass opacities.

BACKGROUND: Ground glass opacity (GGO) is the main HRCT feature representing alveolitis in systemic sclerosis-associated interstitial lung disease (SSc-ILD), but may also represent other conditions such as atelectasis or edema. It is unclear how much this is affected by the HRCT scan protocol used. We aimed to compare the performance of three different HRCT protocols to evaluate the degree of SSc-ILD related changes. METHODS: Eleven patients with SSc underwent chest HRCT scan by three different protocols: First, a supine scan after lying down for 15 minutes, then two scans in alternating order: A prone position scan, and a supine position scan after performing 10 deep breaths using a positive expiratory pressure (PEP) device. The HRCT scans were evaluated by the Warrick score system for ILD-related findings. RESULTS: The three HRCT protocols were compared and resulted in different mean (95% CI) Warrick scores: 9.4 (5.3-13.4) in supine after rest; 7.5 (95% CI 3.8-11.1) in prone and 7.6 (95% CI 4.2-11.1) in supine after PEP. When comparing supine after rest to prone and supine after PEP, the latter two scans had a significantly lower score (p = 0.001 for both comparisons). In all cases, only sub-scores for ground glass opacities differed, while sub-scores for fibrosis-related changes did not change. CONCLUSIONS: Different HRCT scan protocols significantly altered the Warrick severity score for SSc-ILD findings, primarily because of changes in ground glass opacities. These differences may be clinically meaningful.

The burden and impact of chronic cough in severe disease.

PURPOSE OF REVIEW: Chronic cough is common in severe diseases, such as COPD, interstitial lung disease, lung cancer and heart failure, and has a negative effect on quality of life. In spite of this, patients with cough sometimes feel their cough is neglected by healthcare workers. This review aims to briefly describe cough mechanisms, highlight the burden chronic cough can be for the individual, and the clinical impact of chronic cough. RECENT FINDINGS: Chronic cough is likely caused by different mechanisms in different diseases, which may have therapeutic implications. Chronic cough, in general, has a significant negative effect on quality of life, both with and without a severe comorbid disease. It can lead to social isolation, recurrent depressive episodes, lower work ability, and even conditions such as urinary incontinence. Cough may also be predictive of more frequent exacerbations among patients with COPD, and more rapid lung function decline in idiopathic pulmonary fibrosis. Cough is sometimes reported by patients to be underappreciated by healthcare. SUMMARY: Chronic cough has a significant negative impact on quality of life, irrespective of diagnosis. Some differences are seen between patients with and without severe disease. Healthcare workers need to pay specific attention to cough, especially patients with severe disease.

Surfactant protein A in particles in exhaled air and plasma.

Respiratory tract lining fluid (RTLF) is an important component of the lung epithelial barrier. Pathological changes in RTLF may cause increased permeability of the epithelial barrier, but changes within RTLF are difficult to assess non-invasively. The aim of this study was to explore if the use of the non-invasive measurement technique, Particles in Exhaled Air (PEx) and blood test were useful in assessing epithelial barrier, and if cigarette smoking affects the relationship. In a general population subcohort from the European Community Respiratory Health Survey III in Iceland (n = 112), we collected RTLF droplets using the PEx technique, in conjunction with blood samples and questionnaire data. We measured surfactant protein A (SP-A) in the collected plasma and PEx samples. Participants were defined as healthy if they did not currently have asthma, were non-smokers and had forced expiratory volume in one second ≥ 80% of predicted value. Of the 112 participants, 97 were healthy and 15 were current smokers. There was no correlation between plasma and PEx SP-A levels. However, the ratio of plasma to PEx SP-A was significantly higher in smokers compared to healthy subjects. The lack of correlation between PEx and plasma SP-A in healthy participants, indicates that SP-A in plasma does not diffuse freely over the lung epithelial barrier. However, the lung epithelial barrier may be injured by smoking, leading to diffusion of SP-A across the barrier into the bloodstream, causing an increased ratio of plasma to PEx SP-A.

Insufficient sleep and new onset of nocturnal gastroesophageal reflux among women: a longitudinal cohort study.

STUDY OBJECTIVES: Whether short or insufficient sleep are risk factors for new-onset nocturnal gastroesophageal reflux (nGER). METHODS: In this 10-year longitudinal study, adult general-population women in Uppsala, Sweden, answered questionnaires on sleep, nGER, and other conditions on 2 occasions. Participants at baseline totaled 6,790, while participants at follow-up totaled 4,925. "Short sleep" was defined as sleeping < 6 hours/night and "insufficient sleep" was defined as reporting an average actual sleep duration below 80% of the self-estimated need for sleep duration but without "short sleep." nGER was defined as reporting heartburn or acid reflux after going to bed sometimes, often, or very often. The confounding factors-age, body mass index, physical activity, caffeine intake, smoking habits, alcohol dependence, depression, anxiety, and snoring-were defined from the questionnaire. RESULTS: At baseline, 839 participants reported short sleep and 1,079 participants were defined as having insufficient sleep. Both participants with insufficient sleep and short sleep had nGER more often than those with sufficient sleep (26% vs 17% vs 10%, respectively). At follow-up, a new onset of nGER was twice as common among those with insufficient or short sleep at baseline and follow-up, compared with those with sufficient sleep at baseline and follow-up, even after adjusting for confounding factors (odds ratio 2.0 [1.5-2.8], P < .001). CONCLUSIONS: Insufficient sleep and short sleep are associated with nGER. Persistent insufficient and/or short sleep independently increases the risk of developing nGER over a 10-year follow-up. Women seeking treatment for nGER should be questioned about their sleep habits to identify insufficient sleep as a possible causative factor. CITATION: Emilsson OI, Al Yasiry H, Theorell-Haglöw J, Ljunggren M, Lindberg E. Insufficient sleep and new onset of nocturnal gastroesophageal reflux among women: a longitudinal cohort study. J Clin Sleep Med. 2022;18(7):1731-1737.

Obstructive sleep apnea is an independent risk factor for severe COVID-19: a population-based study.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) has been proposed as a risk factor for severe COVID-19. Confounding is an important consideration as OSA is associated with several known risk factors for severe COVID-19. Our aim was to assess the association of OSA with hospitalization due to COVID-19 using a population-based cohort with detailed information on OSA and comorbidities. METHODS: Included were all community-dwelling Icelandic citizens 18 years of age and older diagnosed with SARS-CoV-2 infection in 2020. Data on demographics, comorbidities, and outcomes of COVID-19 was obtained from centralized national registries. Diagnosis of OSA was retrieved from the centralized Sleep Department Registry at Landspitali - The National University Hospital. Severe COVID-19 was defined as the composite outcome of hospitalization and death. The associations between OSA and the outcome were expressed as odds ratios (OR) with 95% confidence intervals (95% CI), calculated using logistic regression models and inverse probability weighting. RESULTS: A total of 4,756 individuals diagnosed with SARS-CoV-2 infection in Iceland were included in the study (1.3% of the Icelandic population), of whom 185 had a diagnosis of OSA. In total, 238 were hospitalized or died, 38 of whom had OSA. Adjusted for age, sex, and BMI, OSA was associated with poor outcome (OR 2.2, 95% CI 1.4-3.5). This association was slightly attenuated (OR 2.0, 95% CI 2.0, 1.2-3.2) when adjusted for demographic characteristics and various comorbidities. CONCLUSIONS: OSA was associated with twofold increase in risk of severe COVID-19, and the association was not explained by obesity or other comorbidities.

Bronchodilator response and lung function decline: Associations with exhaled nitric oxide with regard to sex and smoking status.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is a marker of type-2 inflammation used both to support diagnosis of asthma and follow up asthma patients. The associations of FeNO with lung function decline and bronchodilator (BD) response have been studied only scarcely in large populations. OBJECTIVES: To study the association between FeNO and a) retrospective lung function decline over 20 years, and b) lung function response to BD among asthmatic subjects compared with non-asthmatic subjects and with regards to current smoking and sex. METHODS: Longitudinal analyses of previous lung function decline and FeNO level at follow-up and cross-sectional analyses of BD response and FeNO levels in 4257 participants (651 asthmatics) from the European Community Respiratory Health Survey. RESULTS: Among asthmatic subjects, higher percentage declines of FEV1 and FEV1/FVC were associated with higher FeNO levels (p = 0.001 for both) at follow-up. These correlations were found mainly among non-smoking individuals (p = 0.001) and females (p = 0.001) in stratified analyses.Percentage increase in FEV1 after BD was positively associated with FeNO levels in non-asthmatic subjects. Further, after stratified for sex and smoking separately, a positive association was seen between FEV1 and FeNO levels in non-smokers and women, regardless of asthma status. CONCLUSIONS: We found a relationship between elevated FeNO and larger FEV1 decline over 20 years among subjects with asthma who were non-smokers or women. The association between elevated FeNO levels and larger BD response was found in both non-asthmatic and asthmatic subjects, mainly in women and non-smoking subjects.

Association between lung function decline and obstructive sleep apnoea: the ALEC study.

PURPOSE: To study changes in lung function among individuals with a risk of obstructive sleep apnoea (OSA), and if asthma affected this relationship. METHODS: We used data from the European Community Respiratory Health Survey II and III, a multicentre general population study. Participants answered questionnaires and performed spirometry at baseline and 10-year follow-up (n = 4,329 attended both visits). Subjects with high risk for OSA were identified from the multivariable apnoea prediction (MAP) index, calculated from BMI, age, gender, and OSA symptoms at follow-up. Asthma was defined as having doctor's diagnosed asthma at follow-up. Primary outcomes were changes in forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) from baseline to follow-up. RESULTS: Among 5108 participants at follow-up, 991 (19%) had a high risk of OSA based on the MAP index. Participants with high OSA risk more often had wheeze, cough, chest tightness, and breathlessness at follow-up than those with low OSA risk. Lung function declined more rapidly in subjects with high OSA risk (low vs high OSA risk [mean ± SD]: FEV1 = - 41.3 ± 24.3 ml/year vs - 50.8 ± 30.1 ml/year; FVC = - 30.5 ± 31.2 ml/year vs - 45.2 ± 36.3 ml/year). Lung function decline was primarily associated with higher BMI and OSA symptoms. OSA symptoms had a stronger association with lung function decline among asthmatics, compared to non-asthmatics. CONCLUSION: In the general population, a high probability of obstructive sleep apnoea was related to faster lung function decline in the previous decade. This was driven by a higher BMI and more OSA symptoms among these subjects. The association between OSA symptoms and lung function decline was stronger among asthmatics.

Prevalence, progression and impact of chronic cough on employment in Northern Europe.

We investigated the prevalence of chronic cough and its association with work ability and sick leave in the general population.Data were analysed from the Respiratory Health In Northern Europe (RHINE) III cohort (n=13 500), of which 11 252 participants had also participated in RHINE II 10 years earlier, a multicentre study in Northern Europe. Participants answered a questionnaire on chronic cough, employment factors, smoking and respiratory comorbidities.Nonproductive chronic cough was found in 7% and productive chronic cough in 9% of the participants. Participants with nonproductive cough were more often female and participants with productive cough were more often smokers and had a higher body mass index (BMI) than those without cough. Participants with chronic cough more often reported >7 days of sick leave in the preceding year than those without cough ("nonproductive cough" 21% and "productive cough" 24%; p<0.001 for comparisons with "no cough" 13%). This pattern was consistent after adjusting for age, sex, BMI, education level, smoking status and comorbidities. Participants with chronic cough at baseline reported lower work ability and more often had >7 days of sick leave at follow-up than those without cough. These associations remained significant after adjusting for cough at follow-up and other confounding factors.Chronic cough was found in around one in six participants and was associated with more sick leave. Chronic cough 10 years earlier was associated with lower work ability and sick leave at follow-up. These associations were not explained by studied comorbidities. This indication of negative effects on employment from chronic cough needs to be recognised.

Snoring and nocturnal reflux: association with lung function decline and respiratory symptoms.

INTRODUCTION: The study aim was to examine the association of snoring and nocturnal gastro-oesophageal reflux (nGOR) with respiratory symptoms and lung function, and if snoring and/or nGOR associated with a steeper decline in lung function. METHODS: Data from the third visit of the European Community Respiratory Health Survey (ECRHS) was used for cross-sectional analysis. Pre- and post-bronchodilator spirometry was performed, and information on sleep, nGOR and respiratory symptoms was collected (n=5715). Habitual snoring and nGOR were assessed by questionnaire reports. Pre-bronchodilator spirometry from ECRHS I, II and III (20 years follow-up) were used to analyse lung function changes by multivariate regression analysis. RESULTS: Snoring and nGOR were independently associated with a higher prevalence of wheeze, chest tightness, breathlessness, cough and phlegm. The prevalence of any respiratory symptom was 79% in subjects with both snoring and nGOR versus 56% in those with neither (p<0.001). Subjects with both snoring and nGOR had more frequent exacerbations (adjusted prevalence 32% versus 19% among "no snoring, no nGOR", p=0.003). Snoring but not nGOR was associated with a steeper decline in forced expiratory volume in 1 s over 10 years after adjusting for confounding factors (change in % predicted -5.53, versus -4.58 among "no snoring", p=0.04) and forced vital capacity (change in % predicted -1.94, versus -0.99 among "no snoring", p=0.03). CONCLUSIONS: Adults reporting both habitual snoring and nGOR had more respiratory symptoms and more frequent exacerbations of these symptoms. Habitual snoring was associated with a steeper decline in lung function over time.

Respiratory symptoms, sleep-disordered breathing and biomarkers in nocturnal gastroesophageal reflux.

BACKGROUND: Nocturnal gastroesophageal reflux (nGER) is associated with respiratory symptoms and sleep-disordered breathing (SDB), but the pathogenesis is unclear. We aimed to investigate the association between nGER and respiratory symptoms, exacerbations of respiratory symptoms, SDB and airway inflammation. METHODS: Participants in the European Community Respiratory Health Survey III in Iceland with nGER symptoms (n = 48) and age and gender matched controls (n = 42) were studied by questionnaires, exhaled breath condensate (EBC), particles in exhaled air (PEx) measurements, and a home polygraphic study. An exacerbation of respiratory symptoms was defined as an episode of markedly worse respiratory symptoms in the previous 12 months. RESULTS: Asthma and bronchitis symptoms were more common among nGER subjects than controls (54 % vs 29 %, p = 0.01; and 60 % vs 26 %, p < 0.01, respectively), as were exacerbations of respiratory symptoms (19 % vs 5 %, p = 0.04). Objectively measured snoring was more common among subjects with nGER than controls (snores per hour of sleep, median (IQR): 177 (79-281) vs 67 (32-182), p = 0.004). Pepsin (2.5 ng/ml (0.8-5.8) vs 0.8 ng/ml (0.8-3.6), p = 0.03), substance P (741 pg/ml (626-821) vs 623 pg/ml (562-676), p < 0.001) and 8-isoprostane (3.0 pg/ml (2.7-3.9) vs 2.6 pg/ml (2.2-2.9), p = 0.002) in EBC were higher among nGER subjects than controls. Albumin and surfactant protein A in PEx were lower among nGER subjects. These findings were independent of BMI. CONCLUSION: In a general population sample, nGER is associated with symptoms of asthma and bronchitis, as well as exacerbations of respiratory symptoms. Also, nGER is associated with increased respiratory effort during sleep. Biomarker measurements in EBC, PEx and serum indicate that micro-aspiration and neurogenic inflammation are plausible mechanisms.

Definition of nocturnal gastroesophageal reflux for studies on respiratory diseases.

OBJECTIVE: Nocturnal gastroesophageal reflux (nGER) has been associated with respiratory diseases. Our aim was to study a questionnaire method to identify nGER subjects with respiratory involvement in a general population. MATERIAL AND METHODS: A subgroup of Icelandic participants in the European Community Respiratory Health Survey III (ECRHS III) reporting symptoms of nGER (n = 48) as well as age and gender paired controls (n = 42) were studied further by a structured interview, questionnaires, laryngeal fibrescopy, and exhaled breath condensate. A subgroup underwent 24-h oesophageal pH impedance (24-h MII-pH) measurements. Symptoms of nGER were assessed with a modified version of the reflux disease questionnaire (RDQ), where symptoms were divided into daytime and nocturnal. A report of nGER both at baseline and at follow-up was defined as persistent nGER. RESULTS: Participants reporting persistent nGER had significantly more signs of laryngopharyngeal reflux according to the reflux finding score than those without nGER (Mean ± SD: 5.1 ± 2.3 vs. 3.9 ± 2.2, p = 0.02). Of the 16 persistent nGER subjects that underwent 24-h MII-pH, 11 had abnormal gastroesophageal reflux, but none of three control subjects (69% vs. 0%). Pepsin was more commonly found in exhaled breath condensate in the nGER group (67% vs. 45%, p = 0.04). CONCLUSIONS: Participants with nGER symptoms at least once a month, reported on two occasions, had a high level of positive 24-h MII-pH measurements, laryngeal inflammation and pepsin in exhaled breath condensate. This nGER definition identified a representable group for studies on nGER and respiratory diseases in a general population.