Lower airway microbiota in COPD and healthy controls.

BACKGROUND: The lower airway microbiota in patients with chronic obstructive pulmonary disease (COPD) are likely altered compared with the microbiota in healthy individuals. Information on how the microbiota is affected by smoking, use of inhaled corticosteroids (ICS) and COPD severity is still scarce. METHODS: In the MicroCOPD Study, participant characteristics were obtained through standardised questionnaires and clinical measurements at a single centre from 2012 to 2015. Protected bronchoalveolar lavage samples from 97 patients with COPD and 97 controls were paired-end sequenced with the Illumina MiSeq System. Data were analysed in QIIME 2 and R. RESULTS: Alpha-diversity was lower in patients with COPD than controls (Pielou evenness: COPD=0.76, control=0.80, p=0.004; Shannon entropy: COPD=3.98, control=4.34, p=0.01). Beta-diversity differed with smoking only in the COPD cohort (weighted UniFrac: permutational analysis of variance R2=0.04, p=0.03). Nine genera were differentially abundant between COPD and controls. Genera enriched in COPD belonged to the Firmicutes phylum. Pack years were linked to differential abundance of taxa in controls only (ANCOM-BC (Analysis of Compositions of Microbiomes with Bias Correction) log-fold difference/q-values: Haemophilus -0.05/0.048; Lachnoanaerobaculum -0.04/0.03). Oribacterium was absent in smoking patients with COPD compared with non-smoking patients (ANCOM-BC log-fold difference/q-values: -1.46/0.03). We found no associations between the microbiota and COPD severity or ICS. CONCLUSION: The lower airway microbiota is equal in richness in patients with COPD to controls, but less even. Genera from the Firmicutes phylum thrive particularly in COPD airways. Smoking has different effects on diversity and taxonomic abundance in patients with COPD compared with controls. COPD severity and ICS use were not linked to the lower airway microbiota.

General and orofacial symptoms associated with acute and long COVID in 80- and 90-year-old Swedish COVID-19 survivors.

OBJECTIVES: To describe acute and long COVID-19 symptoms among older elderly Swedes and to find predictive factors for the development symptoms associated with acute and long COVID. MATERIAL AND METHODS: A questionnaire about general and oral health was mailed to all 80-year-olds (born 1942, n = 6299) and 90-year-olds (born 1932, n = 1904) in two Swedish counties. Participants reporting COVID-19 were asked to complete an additional questionnaire. RESULTS: Overall response rate was 66 % (n = 5375). Affirmative responses to having been sick/tested positive for COVID-19 were reported by 577 persons. Response rate to the COVID-19 questionnaire was 49 %. The majority (88 %) reported some general symptoms during the acute stage while 44 % reported orofacial symptom/s. Reporting of any form of long-COVID general symptoms was 37 and 35 % for orofacial symptoms. Predictive factors for contracting COVID-19 (based on self-report from 2017) were living in elderly housing/senior care facility (OR 1.6, CI 1.0-2.3), large number (>10) of weekly social contacts (OR 1.5, CI 1.3-1.9), being married (OR 1.4, CI 1.1-1.7) and high school/university education (OR 1.3 CI 1.1-1-6). The highest odds ratio for general symptoms of long-COVID were a single complete denture (OR 5.0, CI 2.0-12.3), reporting bad breath (OR 3.7, CI 1.9-7.2) and daytime dry mouth (OR 2.2, CI 1.1-4.2). Regarding long-COVID orofacial symptoms, the highest risk factors were bad breath (OR 3.8, CI 1.9-7.5) and a single complete denture in one jaw (OR 3.4, CI 1.2-9.8). CONCLUSION: Long-COVID general and orofacial symptoms are common among older elderly COVID-19 survivors CLINICAL SIGNIFICANCE: Oral microorganisms may be responsible for development of long-COVID symptoms. Health personnel managing COVID-19 patients should carefully examine dental status, especially in those having acrylic-based removable dentures, for oral signs and symptoms. If found, rigorous oral hygiene procedures should be carried out including cleaning/disinfection of the denture.

Association between Covid-19 infection and platypnea-orthodeoxia syndrome.

Introduction and importance: Platypnea-orthodeoxia syndrome is defined as dyspnoea and deoxygenation when changing from a recumbent to an upright position. Post-Covid-19 sequelae can induce or exacerbate pulmonary hypertension and thereby render a previously mild and asymptomatic platypnea-orthodeoxia syndrome to manifest with new or worsening symptoms. Case presentation: The authors present the case of an 80-year-old man who following an episode of moderate-severe Covid-19 infection developed type I respiratory failure that required hospital discharge with long-term oxygen therapy. He had a background history of postural paroxysmal hypoxaemia which had previously raised the suspicion of a right-to-left shunt through either a patent foramen ovale, atrial septal defect or an intrapulmonary arteriovenous malformation. However, given the low burden of symptoms this was not explored further. Following recovery from Covid-19 infection, the patient experienced marked dyspnoea and oxygen desaturation in an upright position that was relieved by a return to a supine position. Discussion and conclusion: Persistent dyspnoea and hypoxia are common symptoms in patients who experience post-Covid-19 syndrome. However, when patients with prior moderate-to-severe Covid-19 illness present with new onset breathlessness and/or desaturation that is worsened in an upright position, platypnea-orthodeoxia syndrome should be considered.

Prevalence and impact of exercise-induced laryngeal obstruction in asthma: a study protocol for a cross-sectional and longitudinal study.

INTRODUCTION: Exercise-induced laryngeal obstruction (EILO) and exercise-induced asthma can cause troublesome respiratory symptoms that can be difficult to distinguish between. Further, there is now a growing appreciation that the two conditions may coexist, complicating the interpretation of symptoms. The primary aim of this study is to investigate the prevalence of EILO in patients with asthma. Secondary aims include evaluation of EILO treatment effects and investigation of comorbid conditions other than EILO in patients with asthma. METHODS AND ANALYSIS: The study will be conducted at Haukeland University Hospital and Voss Hospital in Western Norway, and enrol 80-120 patients with asthma and a control group of 40 patients without asthma. Recruitment started in November 2020, and data sampling will continue until March 2024. Laryngeal function will be assessed at baseline and at a 1-year follow-up, using continuous laryngoscopy during high-intensity exercise (CLE). Immediately after the EILO diagnosis is verified, patients will be treated with standardised breathing advice guided by visual biofeedback from the laryngoscope video screen. The primary outcome will be the prevalence of EILO in patients with asthma and control participants. Secondary outcomes include changes in CLE scores, asthma-related quality of life, asthma control and number of the asthma exacerbations, as assessed between baseline and the 1-year follow-up. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Regional Committee for Medical and Health Research Ethics, Western Norway, (ID number 97615). All participants will provide signed informed consent before enrolment. The results will be presented in international journals and conferences. TRIAL REGISTRATION NUMBER: NCT04593394.

Impact of Initiating Biologics in Patients With Severe Asthma on Long-Term Oral Corticosteroids or Frequent Rescue Steroids (GLITTER): Data From the International Severe Asthma Registry.

BACKGROUND: Effectiveness of biologics has neither been established in patients with high oral corticosteroid exposure (HOCS) nor been compared with effectiveness of continuing with HOCS alone. OBJECTIVE: To examine the effectiveness of initiating biologics in a large, real-world cohort of adult patients with severe asthma and HOCS. METHODS: This was a propensity score-matched, prospective cohort study using data from the International Severe Asthma Registry. Between January 2015 and February 2021, patients with severe asthma and HOCS (long-term OCSs for ≥1 year or ≥4 courses of rescue OCSs within a 12-month period) were identified. Biologic initiators were identified and, using propensity scores, matched 1:1 with noninitiators. The impact of biologic initiation on asthma outcomes was assessed using generalized linear models. RESULTS: We identified 996 matched pairs of patients. Both groups improved over the 12-month follow-up period, but improvement was greater for biologic initiators. Biologic initiation was associated with a 72.9% reduction in the average number of exacerbations per year versus noninitiators (0.64 vs 2.06; rate ratio, 0.27 [95% CI, 0.10-0.71]). Biologic initiators were 2.2 times more likely than noninitiators to take a daily long-term OCS dose of less than 5 mg (risk probability, 49.6% vs 22.5%; P = .002) and had a lower risk of asthma-related emergency department visits (relative risk, 0.35 [95% CI, 0.21-0.58]; rate ratio, 0.26 [0.14-0.48]) and hospitalizations (relative risk, 0.31 [95% CI, 0.18-0.52]; rate ratio, 0.25 [0.13-0.48]). CONCLUSIONS: In a real-world setting, including patients with severe asthma and HOCS from 19 countries, and within an environment of clinical improvement, initiation of biologics was associated with further improvements across multiple asthma outcomes, including exacerbation rate, OCS exposure, and health care resource utilization.

Prevalence and management of severe asthma in the Nordic countries: findings from the NORDSTAR cohort.

Background: Real-life evidence on prevalence and management of severe asthma is limited. Nationwide population registries across the Nordic countries provide unique opportunities to describe prevalence and management patterns of severe asthma at population level. In nationwide register data from Sweden, Norway and Finland, we examined the prevalence of severe asthma and the proportion of severe asthma patients being managed in specialist care. Methods: This is a cross-sectional study based on the Nordic Dataset for Asthma Research (NORDSTAR) research collaboration platform. We identified patients with severe asthma in adults (aged ≥18 years) and in children (aged 6-17 years) in 2018 according to the European Respiratory Society/American Thoracic Society definition. Patients managed in specialist care were those with an asthma-related specialist outpatient contact (only available in Sweden and Finland). Results: Overall, we identified 598 242 patients with current asthma in Sweden, Norway and Finland in 2018. Among those, the prevalence of severe asthma was 3.5%, 5.4% and 5.2% in adults and 0.4%, 1.0%, and 0.3% in children in Sweden, Norway and Finland, respectively. In Sweden and Finland, 37% and 40% of adult patients with severe asthma and two or more exacerbations, respectively, were managed in specialist care; in children the numbers were 56% and 41%, respectively. Conclusion: In three Nordic countries, population-based nationwide data demonstrated similar prevalence of severe asthma. In children, severe asthma was a rare condition. Notably, a large proportion of patients with severe asthma were not managed by a respiratory specialist, suggesting the need for increased recognition of severe asthma in primary care.

The lower airways microbiota and antimicrobial peptides indicate dysbiosis in sarcoidosis.

BACKGROUND: The role of the pulmonary microbiome in sarcoidosis is unknown. The objectives of this study were the following: (1) examine whether the pulmonary fungal and bacterial microbiota differed in patients with sarcoidosis compared with controls; (2) examine whether there was an association between the microbiota and levels of the antimicrobial peptides (AMPs) in protected bronchoalveolar lavage (PBAL). METHODS: Thirty-five sarcoidosis patients and 35 healthy controls underwent bronchoscopy and were sampled with oral wash (OW), protected BAL (PBAL), and left protected sterile brushes (LPSB). The fungal ITS1 region and the V3V4 region of the bacterial 16S rRNA gene were sequenced. Bioinformatic analyses were performed with QIIME 2. The AMPs secretory leucocyte protease inhibitor (SLPI) and human beta defensins 1 and 2 (hBD-1 and hBD-2), were measured in PBAL by enzyme-linked immunosorbent assay (ELISA). RESULTS: Aspergillus dominated the PBAL samples in sarcoidosis. Differences in bacterial taxonomy were minor. There was no significant difference in fungal alpha diversity between sarcoidosis and controls, but the bacterial alpha diversity in sarcoidosis was significantly lower in OW (p = 0.047) and PBAL (p = 0.03) compared with controls. The beta diversity for sarcoidosis compared with controls differed for both fungi and bacteria. AMP levels were significantly lower in sarcoidosis compared to controls (SLPI and hBD-1: p < 0.01). No significant correlations were found between alpha diversity and AMPs. CONCLUSIONS: The pulmonary fungal and bacterial microbiota in sarcoidosis differed from in controls. Lower antimicrobial peptides levels were seen in sarcoidosis, indicating an interaction between the microbiota and the innate immune system. Whether this dysbiosis represents a pathogenic mechanism in sarcoidosis needs to be confirmed in experimental studies. Video Abstract.

Characterization of Patients in the International Severe Asthma Registry with High Steroid Exposure Who Did or Did Not Initiate Biologic Therapy.

Background: Many severe asthma patients with high oral corticosteroid exposure (HOCS) often do not initiate biologics despite being eligible. This study aimed to compare the characteristics of severe asthma patients with HOCS who did and did not initiate biologics. Methods: Baseline characteristics of patients with HOCS (long-term maintenance OCS therapy for at least 1 year, or ≥4 courses of steroid bursts in a year) from the International Severe Asthma Registry (ISAR; https://isaregistries.org/), who initiated or did not initiate biologics (anti-lgE, anti-IL5/5R or anti-IL4R), were described at the time of biologic initiation or registry enrolment. Statistical relationships were tested using Pearson's chi-squared tests for categorical variables, and t-tests for continuous variables, adjusting for potential errors in multiple comparisons. Results: Between January 2015 and February 2021, we identified 1412 adult patients with severe asthma from 19 countries that met our inclusion criteria of HOCS, of whom 996 (70.5%) initiated a biologic and 416 (29.5%) did not. The frequency of biologic initiation varied across geographical regions. Those who initiated a biologic were more likely to have higher blood eosinophil count (483 vs 399 cells/µL, p=0.003), serious infections (49.0% vs 13.3%, p<0.001), nasal polyps (35.2% vs 23.6%, p<0.001), airflow limitation (56.8% vs 51.8%, p=0.013), and uncontrolled asthma (80.8% vs 73.2%, p=0.004) despite greater conventional treatment adherence than those who did not start a biologic. Both groups had similar annual asthma exacerbation rates in the previous 12 months (5.7 vs 5.3, p=0.147). Conclusion: Around one third of severe HOCS asthma patients did not receive biologics despite a similar high burden of asthma exacerbations as those who initiated a biologic therapy. Other disease characteristics such as eosinophilic phenotype, serious infectious events, nasal polyps, airflow limitation and lack of asthma control appear to dictate biologic use.

Cardiovascular remodeling in obstructive sleep apnea: focus on arterial stiffness, left ventricular geometry and atrial fibrillation.

INTRODUCTION: Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder that is associated with increased risk of cardiovascular disease. The main interest of this clinical review is to discuss the cardiovascular consequences of OSA with a special focus on left ventricular (LV) function and structure, arterial stiffness and atrial fibrillation. AREA COVERED: We present an overview of the definition, prevalence, and risk factors of OSA and outline the association between OSA and cardiovascular complications. We then briefly discuss echocardiographic assessment in OSA with focus on the left atrium and LV. Finally, we highlight the importance of adherence to continuous positive airway pressure (CPAP) therapy with regard to reducing the risk of cardiovascular disease. EXPERT COMMENTARY: Although OSA has a strong association with cardiovascular complications, it is often underdiagnosed and undertreated. Patients with resistant hypertension and atrial fibrillation with poor therapeutic success after cardioversion or catheter ablation should be more often screened for OSA. Patients with nocturnal adverse cardiovascular events (stroke, arrhythmias, angina, coronary events) should be closely assessed with regard to OSA, and if confirmed, timely treated by lifestyle modification, CPAP, and aggressive antihypertensive treatment. Adherence to CPAP in OSA patients is essential in terms of reducing the risk of cardiovascular events.

Clinical information predicting severe obstructive sleep apnea: A cross-sectional study of patients waiting for sleep diagnostics.

INTRODUCTION: Obstructive sleep apnea (OSA) is highly prevalent with serious health consequences. Demand for diagnostic studies is high, in many countries exceeding capacity. PURPOSE: The objective of this cross-sectional study was to identify predictors of severe OSA among patients on waiting lists for sleep studies, to better prioritize time to examinations. METHODS: The sample comprised 3646 patients (30.3% women) referred to a university clinic in Western Norway with suspected OSA. All patients underwent respiratory polygraphy. Severe OSA was defined by an apnea-hypopnea index ≥30. Information on symptoms (snoring, breathing cessations, daytime sleepiness) and medical history was collected with questionnaires, including prior diagnosis of angina, myocardial infarction, stroke, hypertension, depression or diabetes. Blood pressure was measured with thresholds of 90 and 140 mmHg defining diastolic and systolic hypertension. RESULTS: 15.7% had severe OSA. In multivariate logistic regression analysis, factors positively associated with severe OSA were increasing age, male sex, snoring, breathing cessations, BMI ≥30, diastolic hypertension, self-reported history of hypertension, and self-reported myocardial infarction. A prediction score (range 0-5) devised from 5 of these items (age ≥50, snoring, breathing cessations, BMI ≥30, and self-reported hypertension) had a sensitivity of 96.2% and a negative predictive value of 97.1% for severe OSA, when a score ≥2 was set as cut-off. CONCLUSIONS: Based on a prediction score derived from simple, easily available data, patients unlikely to suffer from severe OSA can be identified, and thus facilitate more urgent consideration of patients more likely to have severe OSA.

Association of Excessive Sleepiness, Pathological Fatigue, Depression, and Anxiety With Different Severity Levels of Obstructive Sleep Apnea.

Objective: The aim of this study was to investigate possible associations between obstructive sleep apnea and fatigue. This naturally led to considering the association between OSA and excessive sleepiness, depression, and anxiety. Background: OSA is a highly prevalent sleep disorder, associated with a risk of hypertension, cardiovascular events, daytime sleepiness, poor cognitive function, and sudden death during sleep. Both excessive sleepiness, fatigue, and symptoms of depression are frequently reported. Method: 5,464 patients referred to a university hospital for obstructive sleep apnea underwent standard respiratory polygraphy. The severity of OSA was defined as either mild, moderate, or severe, using the apnea-hypopnea index. Validated questionnaires were used to assess excessive sleepiness, pathological fatigue, depression, and anxiety. Results: Nearly 70% of the patients were men, and median age was 50 (range: 16-89) years. One in three had moderate-to-severe OSA (AHI ≥ 15). Excessive sleepiness and pathological fatigue were present in 43 and 39%, respectively. The prevalence of possible depression and anxiety was 19 and 28%, respectively. The proportion of patients with male sex, obesity, and excessive sleepiness increased with the severity of OSA. In contrast, the proportion of patients with pathological fatigue did not increase with OSA severity, and there was a decrease in depression and anxiety with increasing OSA severity. Conclusion: Our study reports that pathological fatigue, as well as anxiety and depression, did not increase with OSA severity, whereas excessive sleepiness did. Knowledge concerning conditions related to OSA severity may be indicative of pretest probability of OSA and thus change the priority for polygraphy. Furthermore, the high prevalence rates of fatigue, anxiety, and depression among these patients warrant further investigations.

Characteristics of hypertension and arterial stiffness in obstructive sleep apnea: A Scandinavian experience from a prospective study of 6408 normotensive and hypertensive patients.

The impact of obstructive sleep apnea (OSA) on arterial stiffness is less studied. We aimed to investigate the prevalence and covariates of increased pulse pressure (PP), a surrogate marker of arterial stiffness, in the entire study population as well as in separate analyses in normotensive and hypertensive patients. Further, we also explored the impact of smoking on brachial BP in hypertensive patients. Between 2012 and 2019, a total of 6408 participants with suspected OSA underwent a standard out-of-center respiratory polygraphy. OSA was defined by an apnea-hypopnea index (AHI) ≥15/h regardless of symptoms. PP ≥60 mmHg was used as a surrogate marker of increased arterial stiffness. Mean age was 49.3±13.7 years, 69.4% were male, and 34.5% had OSA. The prevalence of hypertension was 70.8% in OSA and 46.7% in No-OSA (AHI < 15/h) controls (P < .0001). Hypertension was controlled (clinic BP < 140/90 mmHg) in 45.5% and uncontrolled in 54.5% (P < .001). Mean PP was 50±12 mmHg in smokers and 52±12 mmHg in non-smokers (P = .001). Increased PP was found in 24.2% of the entire study population and was higher in patients with OSA compared to No-OSA group (27.5% vs 22.4%, P < .0001). In an unadjusted logistic regression model, OSA was associated with a 1.3-fold higher risk of having increased PP (95% CI 1.16-1.48, P < .001). In a multivariable-adjusted model, higher age, male sex, and history of hypertension, but not OSA (OR 0.89; 95% CI 0.77-1.02, P = .104) were associated with increased PP. In this large study of nearly 6500 participants who were referred with suspected OSA, one-third were diagnosed with OSA and a quarter had increased arterial stiffness by elevated brachial PP. Hypertension but not OSA per se was associated with increased arterial stiffness. Hypertension was highly prevalent and poorly controlled.

The lower airways microbiome and antimicrobial peptides in idiopathic pulmonary fibrosis differ from chronic obstructive pulmonary disease.

BACKGROUND: The lower airways microbiome and host immune response in chronic pulmonary diseases are incompletely understood. We aimed to investigate possible microbiome characteristics and key antimicrobial peptides and proteins in idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). METHODS: 12 IPF patients, 12 COPD patients and 12 healthy controls were sampled with oral wash (OW), protected bronchoalveolar lavage (PBAL) and right lung protected sterile brushings (rPSB). The antimicrobial peptides and proteins (AMPs), secretory leucocyte protease inhibitor (SLPI) and human beta defensins 1 and 2 (hBD-1 & hBD-2), were measured in PBAL by enzyme linked immunosorbent assay (ELISA). The V3V4 region of the bacterial 16S rDNA gene was sequenced. Bioinformatic analyses were performed with QIIME 2. RESULTS: hBD-1 levels in PBAL for IPF were lower compared with COPD. The predominant phyla in IPF were Firmicutes, Bacteroides and Actinobacteria; Proteobacteria were among top three in COPD. Differential abundance analysis at genus level showed significant differences between study groups for less abundant, mostly oropharyngeal, microbes. Alpha diversity was lower in IPF in PBAL compared to COPD (p = 0.03) and controls (p = 0.01), as well as in rPSB compared to COPD (p = 0.02) and controls (p = 0.04). Phylogenetic beta diversity showed significantly more similarity for IPF compared with COPD and controls. There were no significant correlations between alpha diversity and AMPs. CONCLUSIONS: IPF differed in microbial diversity from COPD and controls, accompanied by differences in antimicrobial peptides. Beta diversity similarity between OW and PBAL in IPF may indicate that microaspiration contributes to changes in its microbiome.

Partner perceptions are associated with objective sensor-measured adherence to oral appliance therapy in obstructive sleep apnea.

The aims of the present prospective clinical study were to determine objective, sensor-measured adherence to a mandibular advancement device (MAD) in patients with obstructive sleep apnea (OSA) and to identify partner-specific adherence-related factors. A total of 77 eligible participants with mild, moderate, or severe OSA and who were non-adherent to continuous positive airway pressure (mean age 56.2 years) participated in the study (32.5% women). The mean (range) observation time between MAD delivery and final follow-up was 8.3 (3.4-16.5) months. The mean apnea-hypopnea index (AHI) was 26.6 events/hr at baseline and 12.5 events/hr at the 8-month follow-up (both p < 0.001). The mean sensor-measured adherence at the 8-month follow-up was 60.1% for ≥4 hr/night of appliance use for ≥5 days/week. Average usage was 6.4 hr/night, when worn. The mean reduction in the AHI was significantly greater in the "good adherence" (Δ 17.4) than the "poor adherence" group (Δ11.0; p < 0.05). From the partner's perspective, the appliance had a positive effect on sharing a bedroom in the good- (55%) compared to the poor-adherence group (25%; p < 0.05) and on their relationship (51.7% versus 17.9%, respectively; p < 0.05). Regression analyses identified the partner's snoring and apneas to be the most significant factor predicting good adherence to MAD (odds ratio 4.4, 95% confidence interval 1.4-14.0). In conclusion, social factors, like partner perceptions, were positively associated with adherence, which indicate that partner's attitudes and support may be a resource that can be utilised to improve adherence in oral appliance treatment of OSA.

Effect of Continuous Positive Airway Pressure on Symptoms and Prevalence of Insomnia in Patients With Obstructive Sleep Apnea: A Longitudinal Study.

OBJECTIVE: Obstructive sleep apnea (OSA) and insomnia are the two most common sleep disorders. Continuous positive airway pressure (CPAP) is considered first-line treatment for OSA. In the present study, we assess the effect of CPAP on symptoms and prevalence of insomnia in patients with OSA. We hypothesized a decrease in insomnia symptoms from CPAP initiation to follow-up, and that this decrease would depend on CPAP adherence. MATERIALS AND METHODS: The sample included 442 patients diagnosed with OSA [mean age 54.9 years (SD = 12.1), 74.4% males] who started treatment with CPAP at a university hospital. OSA was diagnosed according to standard respiratory polygraphy. Mean apnea-hypopnea index (AHI) was 30.1 (SD = 21.1) at baseline. Insomnia was assessed prior to CPAP treatment (baseline) and at follow-up after a median of 19.9 weeks (range 6-52 weeks) with the Bergen Insomnia Scale (BIS). CPAP adherence was defined as an average use of ≥ 4 h per night, whereas non-adherence was defined as < 4 h per night. RESULTS: There was a significant decrease in BIS scores from baseline (mean = 18.8, SD = 9.8) to follow-up (mean = 12.9, SD = 9.9), p < 0.001. Cohen's d(0.65) indicated a moderate effect size. The reduction in BIS scores was depending on CPAP adherence (interaction effect F(1,440) = 12.4, p < 0.001), with larger reduction in the adherent group than in the non-adherent group. The proportion of patients with chronic insomnia was significantly reduced from 51.1% at baseline to 33.0% at follow-up (p < 0.001). CONCLUSION: Overall, there was a significant reduction in insomnia symptoms from baseline to follow-up. The improvement was significant in both adherence groups, but the degree of improvement was larger among patients who were adherent to CPAP. Furthermore, there was a significant reduction in the prevalence of chronic insomnia at follow-up compared to baseline. This suggests that CPAP effectively reduces both the presence of insomnia and the severity of insomnia symptoms in some patients with OSA.

Eosinophilic and Noneosinophilic Asthma: An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort.

BACKGROUND: Phenotypic characteristics of patients with eosinophilic and noneosinophilic asthma are not well characterized in global, real-life severe asthma cohorts. RESEARCH QUESTION: What is the prevalence of eosinophilic and noneosinophilic phenotypes in the population with severe asthma, and can these phenotypes be differentiated by clinical and biomarker variables? STUDY DESIGN AND METHODS: This was an historical registry study. Adult patients with severe asthma and available blood eosinophil count (BEC) from 11 countries enrolled in the International Severe Asthma Registry (January 1, 2015-September 30, 2019) were categorized according to likelihood of eosinophilic phenotype using a predefined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic and clinical characteristics were defined at baseline (ie, 1 year before or closest to date of BEC). RESULTS: One thousand seven hundred sixteen patients with prospective data were included; 83.8% were identified as most likely (grade 3), 8.3% were identified as likely (grade 2), and 6.3% identified as least likely (grade 1) to have an eosinophilic phenotype, and 1.6% of patients showed a noneosinophilic phenotype (grade 0). Eosinophilic phenotype patients (ie, grades 2 or 3) showed later asthma onset (29.1 years vs 6.7 years; P < .001) and worse lung function (postbronchodilator % predicted FEV1, 76.1% vs 89.3%; P = .027) than those with a noneosinophilic phenotype. Patients with noneosinophilic phenotypes were more likely to be women (81.5% vs 62.9%; P = .047), to have eczema (20.8% vs 8.5%; P = .003), and to use anti-IgE (32.1% vs 13.4%; P = .004) and leukotriene receptor antagonists (50.0% vs 28.0%; P = .011) add-on therapy. INTERPRETATION: According to this multicomponent, consensus-driven, and evidence-based eosinophil gradient algorithm (using variables readily accessible in real life), the severe asthma eosinophilic phenotype was more prevalent than previously identified and was phenotypically distinct. This pragmatic gradient algorithm uses variables readily accessible in primary and specialist care, addressing inherent issues of phenotype heterogeneity and phenotype instability. Identification of treatable traits across phenotypes should improve therapeutic precision.

Acoustic pharyngometry - A new method to facilitate oral appliance therapy.

BACKGROUND: There is lack of reliable and accurate methods to predict treatment outcomes of oral appliance (OA) treatment. Acoustic pharyngometry (AP) is a non-invasive technique to evaluate the volume and minimal cross-sectional area of the upper airway, which may prove useful to locate the optimal position of OAs. OBJECTIVE: This retrospective study aimed to evaluate the effect of applying AP to OA treatment of patients with obstructive sleep apnoea (OSA). METHODS: All patients (n = 244) treated with OAs following an AP protocol at two dental clinics between 2013 and 2018 were invited to participate. A total of 129 patients accepted the invitation, and 120 patients (75 men, 45 women) were included in the analyses. Mean baseline age, BMI and apnoea hypopnea index (AHI) were 59.1 ± 0.9 years, 27.8 ± 0.4 and 21.9 ± 1.1, respectively. Mean follow-up time was 318 ± 24 days. RESULTS: AHI at follow-up was 6.4 ± 0.7, resulting in a treatment success rate of 86.7% (≥50% reduction of baseline AHI). The number of failures (<50% reduction of baseline AHI) did not differ significantly among patients with mild, moderate and severe OSA. 87.6% of the patients reported OA usage every night, and 95.5% reported > 5 hours usage per night, when worn. CONCLUSION: The AP protocol applied seems to contribute to the excellent effect of OA treatment in this study. Further research on the application of AP in OA treatment is necessary in order to clarify its possible beneficial contribution to improving OA therapy.

Effect of continuous positive airway pressure on symptoms of anxiety and depression in patients with obstructive sleep apnea.

PURPOSE: The objective was to assess the effect of continuous positive airway pressure (CPAP) on symptoms of anxiety and depression in patients with obstructive sleep apnea (OSA). We hypothesized a decrease in symptoms at follow-up, but that improvement relied on CPAP adherence. METHODS: The sample comprised 468 patients (mean age 55.5 years (SD = 12.0), 72% men) with OSA who received CPAP at a Norwegian hospital. OSA was diagnosed according to standard respiratory polygraphy. Mean baseline respiratory event index (REI) was 28.4 (SD = 20.6). Symptoms of anxiety and depression were assessed prior to CPAP treatment and at follow-up after a median of 20 weeks, range 6-52 weeks, with the Hospital Anxiety and Depression Scale (HADS). Patients were classified as CPAP adherent (≥ 4 h per night) or non-adherent (< 4 h per night). RESULTS: There was a significant decrease in anxiety scores from baseline (mean = 5.16, SD = 3.94) to follow-up (mean = 4.76, SD = 3.81), p < 0.001. Similarly, depression scores decreased from baseline (mean = 4.31, SD = 3.66) to follow-up (mean = 3.89, SD = 3.69), p < 0.001. Cohen's d (0.19 and 0.18, respectively) indicated small effect sizes. The reduction in anxiety scores did not depend on CPAP adherence (no interaction effect F(1, 466) = 0.422, p = 0.516), whereas the reduction in depression scores were seen only in the CPAP adherent group (interaction effect F(1, 466) = 7.738, p = 0.006). CONCLUSIONS: We found a decrease in symptoms of anxiety and depression from baseline to follow-up of CPAP treatment. The improvement in symptoms of depression was depending on CPAP adherence. This underlines the importance of adherence for optimal effect of CPAP treatment.