Karl Anders Franklin

Introduction: This study compared sleep quality and insomnia symptoms in individuals with and without asthma and identified potentially treatable traits that could be used to improve sleep in asthma. Methods: This cross-sectional analysis included 28,828 participants (aged 50– 64). Post-bronchodilator forced expiratory volume (FEV₁) and forced vital capacity (FVC) were measured. Questionnaires assessed physician-diagnosed asthma, asthma-related symptoms, exacerbations, allergic rhinitis, chronic rhinosinusitis (CRS), nocturnal breathing disorders and reflux (snoring, sleep apnea, nocturnal gastroesophageal reflux [nGER]), and sleep quality. Insomnia symptoms included difficulties initiating sleep (DIS), difficulties maintaining sleep (DMS), and early morning awakening (EMA). Results: Current asthma was associated with impaired sleep quality (OR=1.56; [95% CI:] 1.39– 1.75), DIS (1.59; [1.40– 1.81]), DMS (1.36; [1.22– 1.51]), EMA (1.31; [1.16– 1.48]), and any insomnia symptom (1.38; [1.25– 1.52]). Among individuals with asthma, allergic rhinitis was linked to impaired sleep quality (1.28; [1.01– 1.62]), while CRS, asthma symptoms, exacerbations, snoring, sleep apnea and nGER were associated with impaired sleep quality and insomnia symptoms. Those with uncontrolled asthma, CRS, or nocturnal breathing disorders and reflux had higher odds of impaired sleep quality and any insomnia symptom, with the strongest associations in those with all three conditions (5.68; [3.47– 9.29] and 3.63; [2.26– 5.85], respectively). Conclusion: Asthma is associated with impaired sleep quality and insomnia symptoms in middle-aged adults. Our study also indicates that in asthma, impaired sleep quality and insomnia symptoms are linked to three potentially treatable traits, namely lack of asthma control, upper airway disorders, and nocturnal breathing disorders and reflux.

Background: Father's adolescent smoking and overweight affect respiratory health in offspring, suggesting that paternal puberty exposures may influence offspring biological ageing through preconception epigenetic mechanisms. Methods: We analyzed epigenetic age acceleration using four validated epigenetic clocks derived from blood DNA methylation in 892 RHINESSA offspring (mean age 27 years), linked to parental data on smoking and body shapes from RHINE/ECRHS. Linear regression examined parental smoking initiation (≤15 or >15 years) and overweight body shape (childhood/puberty or age 30) in relation to offspring epigenetic age acceleration, adjusting for offspring sex, age and parental socioeconomic status. Sensitivity analyses accounted for offspring smoking and BMI. Results: PCHorvath (β 1.53; 95% CI 0.02, 2.9), PCGrimAge (1.21; 0.03, 2.1), DunedinPACE (0.04; -0.001, 0.1) and PCPhenoAge (1.92; -0.3, 4.2) were accelerated in daughters of fathers who started smoking ≤15 years. Likewise, PCHorvath (2.25; 1.2, 3.3), PCGrimAge (1.36; -0.2, 2.9), DunedinPACE (0.07; 0.01, 0.1) and PCPhenoAge (3.11; 1.8, 4.4) were accelerated in daughters and sons of fathers who had been overweight in childhood and puberty. These results remained largely unchanged after additional adjustments or stratification in sensitivity analyses. No associations were found for maternal smoking or overweight in puberty. Conclusions: Epigenetic ageing is accelerated in offspring of fathers who smoked or were overweight in puberty, independent of offspring lifestyle. These findings suggest that adolescent boys' environment and lifestyle may be critical for next-generation health.

Background: Patients with sleep apnoea are at increased risk of postoperative cardiac and respiratory complications, but its prevalence in patients undergoing abdominal cancer surgery is poorly defined. The aim of this study was to estimate the prevalence of sleep apnoea in patients undergoing colorectal cancer surgery compared with community-based controls, and to assess the utility of symptoms, signs, and the STOP-Bang questionnaire in identifying sleep apnoea. Methods: This prospective observational study included consecutive patients scheduled for colorectal cancer surgery at Umeå University Hospital, Sweden, between 7 January 2015 and 24 May 2020. Overnight polysomnography, including electroencephalogram-based sleep scoring, was undertaken before operation. Prevalence estimates were compared with those of two community-based cohorts from Uppsala, Sweden (female participants from the Sleep and Health in Women cohort; male participants from the Men in Uppsala: A Study of Sleep Apnoea and Cardiometabolic Health cohort). The primary outcome was the prevalence of sleep apnoea. Results: Of 268 eligible patients, 5 were receiving continuous positive airway pressure therapy and 201 underwent successful polysomnography. Moderate-to-severe sleep apnoea was identified in 98 of 206 patients (48 (95% confidence interval 41 to 54)%) undergoing colorectal cancer surgery, with a similar prevalence in men and women. Among 597 community-based controls, moderate-to-severe sleep apnoea was present in 27 (24 to 31)%. After adjustment for age, sex, and body mass index, the odds ratio for moderate-to-severe sleep apnoea in patients with colorectal cancer was 1.57 (95% confidence interval 1.08 to 2.29; P = 0.019). The STOP-Bang questionnaire demonstrated acceptable sensitivity (85 (95% confidence interval 76 to 91)%) but low specificity (42 (33 to 52)%). Conclusion: Approximately half of patients undergoing colorectal cancer surgery have moderate-to-severe sleep apnoea, exceeding the prevalence in community-based controls. Clinical symptoms, signs, and STOP-Bang screening are insufficient to reliably identify affected patients, indicating that overnight sleep apnoea assessment is required in this population.

Objectives: Although continuous positive airway pressure (CPAP) effectively prevents sleep apnea and reduces blood pressure, many patients do not use CPAP every night. This trial investigates cardiovascular effects after sleeping five nights without CPAP. Methods: We randomized 100 patients (67 men and 33 women with a mean age 64 ± 9 years) using CPAP treatment for moderate-to-severe sleep apnea to either withdraw treatment for five nights (n = 50) or to continue with CPAP (n = 50). The primary outcomes were arterial stiffness and 24 h blood pressure. Results: The 24 h SBP increased by a mean of 2.8 mmHg [95% confidence interval (CI) 0.2–5.4 mmHg] (P = 0.035) and DBP increased by a mean of 1.7 mmHg (95% CI 0.1–3.3 mmHg) (P = 0.032) in the group without CPAP compared to the CPAP group. There was a significant effect on blood pressure in women but not in men. In women, SBP increased by 5.1 mmHg (95% CI 1.0–9.5 mmHg) (P = 0.017) and DBP by 2.9 mmHg (95% CI 0.4–5.6 mmHg) (P = 0.029). Arterial stiffness remained unaffected. Secondary outcomes that worsened in patients without CPAP included apnea–hypopnea index, oxygen desaturation index, hemoglobin levels, and daytime sleepiness. Conclusion: Blood pressure is affected after five nights of CPAP interruption, along with a rapid return of sleep apneas, nocturnal hypoxic events, daytime sleepiness and increased hemoglobin levels, but arterial stiffness was not affected. Blood pressure was affected in women only, suggesting a sex-related CPAP effect on blood pressure.

Purpose: The effect of mandibular advancement device therapy on daytime sleepiness remains unclear. Here, we evaluate the effect of a mandibular advancement device on daytime sleepiness using the Karolinska Sleepiness Scale. Methods: We randomized 88 snoring patients with an apnea-hypopnea index < 30 and daytime sleepiness to a mandibular advancement device or a sham device for four months. The Karolinska Sleepiness Scale, which measures grades of sleepiness from 1 (very alert) to 9 (very sleepy), was used for seven consecutive days, four times each day. The results were analyzed with quantile regression at quartiles controlling for baseline, age, body mass index (kg/m²), sex, apnea-hypopnea index, and full-time work. Results: The Karolinska Sleepiness Scale score was lower with the mandibular advancement device than with the sham device at specific time intervals. The positive effect of mandibular advancement device therapy occurred at wake up and before lunch during the whole week and before lunch on weekdays at the middle quartile. The adjusted differences between the interventions favored mandibular advancement device therapy by almost one unit and normalized the Karolinska Sleepiness Scale scores at wake up and before lunch. In addition, there were positive effects of mandibular advancement device therapy before dinner at the highest quartile during the whole week, on weekdays, and on the weekend. Conclusion: Mandibular advancement devices used for snoring and sleep apnea reduce daytime sleepiness, particularly at wake up and before lunch, but provide some benefit before dinner.

Obstructive sleep apnoea (OSA) and its associations with lung function. Background: OSA is highly prevalent and characterised by abnormal respiration during sleep. This large, population-based study aimed to investigate the associations between OSA and lung function in subjects aged 50–64 years. Method: The population-based Swedish CArdioPulmonary bioimage Study includes information on anthropometry, comorbidities and spirometry. The current analysis included data from three centres (Gothenburg, Umeå and Uppsala) on whole-night respiratory polygraphy as a meta-analysis examining the overall effect size of lung function on sleep apnoea severity, expressed as ß-coefficient after stratifying for sex and adjusting for age, waist circumference and smoking status. Results: Data from 9016 participants ( 54% women, age 58±4 years , body mass index 27±4 kg/m ² ) with sleep recordings of good quality were included in the final analysis. Forced expiratory volume during 1 s (FEV ₁ ) ( ß=−0.10 (95% CI −0.16 to −0.03) ), forced vital capacity ( FVC ) ( −0.15 (−0.21 to −0.10) ) and diffusion capacity for carbon monoxide ( DL _CO ) ( −0.08 (−0.10 to −0.05) ) were all negatively associated with the oxygen desaturation index (ODI) and also with per cent of registration with nocturnal oxygen saturation 1 ( −0.86 (−1.36 to −0.36 )) and DL _CO ( −0.47 (−0.60 to −0.35) ). Additionally, a positive association was observed between FEV ₁ ( 0.13 (0.05 to 0.22) ) and DL _CO ( 0.07 (0.04 to 0.09) ) with the mean nocturnal saturation. There was a negative association between DL _CO and apnoea-hypopnoea index , AHI, ( ß=−0.04 (95% CI−0.06 to −0.03) ), while no associations were found between FEV ₁ or FVC and AHI. Conclusion: In OSA, lower lung function is more distinctly associated with the nocturnal hypoxic burden than AHI. Potential lung function impairment should be investigated in OSA patients with a high ODI relative to AHI.

Background: Without evidence, positive expiratory pressure therapy is a part of rehabilitation worldwide to prevent postoperative hypoxia. Reading aloud could be used as an alternative therapy as lung volumes increases while speaking. We aimed to investigate whether reading aloud is superior to positive expiratory pressure therapy for improving oxygen saturation after abdominal surgery. Material and Methods: This crossover randomized controlled trial compared reading a text aloud with positive expiratory pressure therapy in patients on postoperative day 1 or 2 after upper gastrointestinal, colorectal, urological, or gynecological abdominal surgery at Umeå University Hospital, Sweden. The primary outcome was the change in peripheral oxygen saturation compared with baseline at 7 min after the intervention. The secondary outcome was transcutaneous carbon dioxide partial pressure change. Results: This study included 50 patients of which 48 patients were analyzed. Peripheral oxygen saturation rapidly decreased to minimum values below baseline immediately after both interventions and then increased to values above baseline after reading aloud (1%, 95% confidence interval 0.2% to 1%, P = 0.004), but not after positive expiratory pressure therapy (−0.2%, 95% confidence interval −1% to 0.4%, P = 0.436). The difference in oxygen saturation was 1% (95% confidence interval 0.1% to 2%, P = 0.039) at 7 min after termination of the interventions. The interventions reduced transcutaneous carbon dioxide partial pressure by similar amounts. Conclusions: This trial adds to the evidence against the use of positive expiratory pressure therapy after abdominal surgery. It is even slightly better to read aloud.

Objectives To investigate the association of early snus use initiation (≤15 years of age) with asthma and asthma symptoms. Design Cross-sectional analysis of a population-based cohort. Setting Study centres in Norway, Sweden, Iceland, Denmark and Estonia, from 2016 to 2019. Participants 9002 male and female participants above 15 years of age of the Respiratory Health in Northern Europe, Spain and Australia study. Main outcome measures Current asthma and asthma symptoms. Results The median age of study participants was 28 years (range 15–53) and 58% were women. 20% had used snus, 29% men and 14% women. Overall, 26% of males and 14% of females using snus started ≤15 years of age. Early snus use initiation was associated with having three or more asthma symptoms (OR 2.70; 95% CI 1.46 to 5.00) and a higher asthma symptom score (β-coefficient (β) 0.35; 95% CI 0.07 to 0.63) in women. These associations were weak in men (OR 1.23; 95% CI 0.78 to 1.94; β 0.16; 95% CI −0.06 to 0.38, respectively). There was evidence for an association of early snus initiation with current asthma (OR 1.72; 95% CI 0.88 to 3.37 in women; OR 1.31; 95% CI 0.84 to 2.06 in men). A sensitivity analysis among participants without smoking history showed stronger estimates for all three outcomes, in both men and women, statistically significant for three or more asthma symptoms in women (OR 3.28; 95% CI 1.18 to 9.10). Finally, no consistent associations with asthma outcomes were found for starting snus after age 15 years. Conclusions Snus initiation in puberty was associated with higher likelihood of asthma and asthma symptoms, with the highest estimates in females and those without smoking history. These results raise concerns about the health adversities of early snus initiation and emphasise the need for public health initiatives to protect young people from this tobacco product.