Perioperative Continuous Positive Airway Pressure Therapy: A Review With the Emphasis on Randomized Controlled Trials and Obstructive Sleep Apnea.

The perioperative use of continuous positive airway pressure (CPAP) therapy has increased substantially in recent years, particularly in relationship to the treatment of patients with known or suspected obstructive sleep apnea (OSA). OSA is common in the surgical population and is reported as an independent risk factor for postoperative complications, intensive care unit admission, and increased length of hospital stay. A large proportion of OSA patients are undiagnosed at the time of surgery and can therefore not be optimized preoperatively. Nowadays, golden standard treatment of moderate to severe OSA is nightly CPAP at home, often with an autotitration mode. Unfortunately, there are only a handful of randomized clinical trials investigating the effect of preoperative and/or postoperative CPAP treatment in OSA patients, so the perioperative guidelines are based on a combination of randomized clinical trials, observational studies, case studies, and expert opinions. In this review, we have summarized the current evidence regarding the use of perioperative CPAP therapy with an emphasis on patients with OSA. We identified 21 randomized, controlled trials that investigated the effect of CPAP on postoperative physiology and complications in surgical patients. Our review reveals evidence, suggesting that CPAP after surgery improves oxygenation and reduces the need for reintubation and mechanical ventilation after surgery. It is also evident that CPAP reduces apnea and hypopnea frequency and related hypoxemia after surgery. Poor adherence to CPAP in the perioperative setting is a limiting factor in assessing its potential to optimize postoperative cardiorespiratory outcomes. Studies of postoperative outcomes in patients who have previously been prescribed CPAP for OSA and are therefore familiar with its use could help to address this shortcoming, but they are unfortunately lacking. This shortcoming should be addressed in future studies. Furthermore, many of the studies of the postoperative effect of CPAP in OSA patents are small, and therefore, single-center studies and larger randomized, controlled multicenter studies are warranted.

Hypoxic ventilatory response after rocuronium-induced partial neuromuscular blockade in men with obstructive sleep apnoea.

Obstructive sleep apnoea and residual neuromuscular blockade are, independently, known to be risk factors for respiratory complications after major surgery. Residual effects of neuromuscular blocking agents are known to reduce the hypoxic ventilatory response in healthy volunteers. Patients with obstructive sleep apnoea have impaired control of breathing, but it is not known to what extent neuromuscular blocking agents interfere with the regulation of breathing in such patients. In a physiological study in 10 unsedated men with untreated obstructive sleep apnoea, we wished to examine if partial neuromuscular blockade had an effect on hypoxic ventilatory response (isocapnic hypoxia to oxygen saturation of 80%) and hypercapnic ventilatory response (normoxic inspired carbon dioxide 5%). The hypoxic ventilatory response was reduced by 32% (p = 0.016) during residual neuromuscular block (rocuronium to train-of-four ratio 0.7), but the hypercapnic ventilatory response was unaffected. We conclude that neuromuscular blockade specifically depresses peripheral chemosensitivity, and not respiratory muscle function since the hypercapnic ventilatory response was unaffected.

Clinical markers of asthma and IgE assessed in parents before conception predict asthma and hayfever in the offspring.

BACKGROUND: Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans. OBJECTIVE: We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever. METHODS: The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972-2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions. RESULTS: Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11-22 years with information on parental disease activity both before and after birth. CONCLUSION & CLINICAL RELEVANCE: Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever.

Effect of an elastic girdle on lung function, intra-abdominal pressure, and pain after midline laparotomy: a randomized controlled trial.

PURPOSE: Girdles and abdominal binders may reduce pain and stabilize the abdominal wall after laparotomy, but a risk for increased intra-abdominal pressure and decreased lung function is also hypothesized. The aim of this study was to investigate the effect of an abdominal girdle after midline laparotomy in a randomized controlled trial. METHODS: Twenty-three patients undergoing laparotomy were randomized to wear an elastic girdle postoperatively and 25 were randomized to no girdle. Pulmonary function was evaluated with; forced vital capacity (FVC), forced expiratory volume during one second (FEV1), peak expiratory flow (PEF), and cough PEF. Pain was recorded using a visual analog scale (VAS). All patients completed the ventral hernia pain questionnaire (VHPQ) before surgery and at the end of the study. Intra-abdominal pressure was measured via an indwelling urinary catheter. Wound healing was assessed from photographs. RESULTS: FVC, FEV1, PEF, and cough PEF were reduced by about 30 % after surgery, but there were no differences between patients with or without a girdle (ANOVA). Intra-abdominal pressure and wound healing were the same in both groups. Pain was significantly lower on day 5 in the girdle group (p = 0.004). CONCLUSIONS: An individually fitted elastic girdle used after midline laparotomy was found to be safe, as this did not affect lung function, coughing, intra-abdominal pressure, or wound healing. The immediate decline in lung function after surgery is restrictive and due to anesthesia and the surgical procedure. Pain was significantly decreased in the girdle group. The study is registered at ClinicalTrials.gov, number NCT01517217.

Impact of plant shoot architecture on leaf cooling: a coupled heat and mass transfer model.

Plants display a range of striking architectural adaptations when grown at elevated temperatures. In the model plant Arabidopsis thaliana, these include elongation of petioles, and increased petiole and leaf angles from the soil surface. The potential physiological significance of these architectural changes remains speculative. We address this issue computationally by formulating a mathematical model and performing numerical simulations, testing the hypothesis that elongated and elevated plant configurations may reflect a leaf-cooling strategy. This sets in place a new basic model of plant water use and interaction with the surrounding air, which couples heat and mass transfer within a plant to water vapour diffusion in the air, using a transpiration term that depends on saturation, temperature and vapour concentration. A two-dimensional, multi-petiole shoot geometry is considered, with added leaf-blade shape detail. Our simulations show that increased petiole length and angle generally result in enhanced transpiration rates and reduced leaf temperatures in well-watered conditions. Furthermore, our computations also reveal plant configurations for which elongation may result in decreased transpiration rate owing to decreased leaf liquid saturation. We offer further qualitative and quantitative insights into the role of architectural parameters as key determinants of leaf-cooling capacity.

Management of obstructive sleep apnea in Europe.

OBJECTIVES: In Europe, the services provided for the investigation and management of obstructive sleep apnoea (OSA) varies from country to country. The aim of this questionnaire-based study was to investigate the current status of diagnostic pathways and therapeutic approaches applied in the treatment of OSA in Europe, qualification requirements of physicians involved in diagnosis and treatment of OSA, and reimbursement of these services. METHODS: Two questionnaires were sent to 39 physicians in 22 countries in Europe. In order to standardize the responses, the questionnaire was accompanied by an example. RESULTS: Sleep centers from 21 countries (38 physicians) participated. A broad consistency among countries with respect to the following was found: pathways included referral to sleep physicians/sleep laboratories, necessity for objective diagnosis (primarily by polysomnography), use of polygraphic methods, analysis of polysomnography (PSG), indications for positive airway pressure (PAP) therapy, application of standard continuous PAP (CPAP) therapy (100% with an CPAP/APAP ratio of 2.24:1), and the need (90.5%) and management of follow-up. Differences were apparent in reimbursement of the diagnostic procedures and follow-up, in the procedures for PAP titration from home APAP titration with portable sleep apnea monitoring (38.1%) up to hospital monitoring with PSG and APAP (85.7%), and in the qualification requirements of sleep physicians. CONCLUSIONS: Management of OSA in different European countries is similar except for reimbursement rules, qualification of sleep specialists and procedures for titration of the CPAP treatment. A European network (such as the one accomplished by the European Cooperation in Science and Technology [COST] B26 Action) could be helpful for implementing these findings into health-service research in order to standardize management in a cost effective perspective.

Joint effect of obesity and TNFA variability on asthma: two international cohort studies.

Obesity is a risk factor for asthma. Adipose tissue expresses pro-inflammatory molecules including tumour necrosis factor (TNF), and levels of TNF are also related to polymorphisms in the TNF-alpha (TNFA) gene. The current authors examined the joint effect of obesity and TNFA variability on asthma in adults by combining two population-based studies. The European Community Respiratory Health Survey and the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults used comparable protocols, questionnaires and measures of lung function and atopy. DNA samples from 9,167 participants were genotyped for TNFA -308 and lymphotoxin-alpha (LTA) +252 gene variants. Obesity and TNFA were associated with asthma when mutually adjusting for their independent effects (odds ratio (OR) for obesity 2.4, 95% confidence interval (CI) 1.7-3.2; OR for TNFA -308 polymorphism 1.3, 95% CI 1.1-1.6). The association of obesity with asthma was stronger for subjects carrying the G/A and A/A TNFA -308 genotypes compared with the more common G/G genotype, particularly among nonatopics (OR for G/A and A/A genotypes 6.1, 95% CI 2.5-14.4; OR for G/G genotype 1.7, 95% CI 0.8-3.3). The present findings provide, for the first time, evidence for a complex pattern of interaction between obesity, a pro-inflammatory genetic factor and asthma.

TNFA -308G>A in two international population-based cohorts and risk of asthma.

Genetic association studies have related the tumour necrosis factor-alpha gene (TNFA) guanine to adenine substitution of nucleotide -308 (-308G>A) polymorphism to increased risk of asthma, but results are inconsistent. The aim of the present study was to test whether two single-nucleotide polymorphisms, of TNFA and of the lymphotoxin-alpha gene (LTA), are associated with asthma, bronchial hyperresponsiveness and atopy in adults, by combining the results of two large population-based multicentric studies and conducting a meta-analysis of previously published studies. The European Community Respiratory Health Survey (ECRHS) and Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) used comparable protocols, including questionnaires for respiratory symptoms and measures of lung function and atopy. DNA samples from 11,136 participants were genotyped at TNFA -308 and LTA 252. Logistic regression employing fixed and random effects models and nonparametric techniques were used. The prevalence of asthma was 6%. The TNFA -308G>A polymorphism was associated with increased asthma prevalence and with bronchial hyperresponsiveness. No consistent association was found for atopy. The LTA 252A>G polymorphism was not associated with any of the outcomes. A meta-analysis of 17 studies showed an increased asthma risk for the TNFA -308 adenine allele. The tumour necrosis factor-alpha gene nucleotide -308 polymorphism is associated with a moderately increased risk of asthma and bronchial hyperresponsiveness, but not with atopy. These results are supported by a meta-analysis of previously published studies.

What can we learn about asthma and allergy from the follow-up of the RHINE and the ECRHS studies?

OBJECT: The international population-based studies RHINE and ECRHS have provided new insight in the epidemiology and management of asthma, allergy and rhinitis in young adults. The aim of the present review is to focus on longitudinal results with regard incidence and net change of asthma and asthma-like symptoms, risk factors and management of asthma, with special reference to the Nordic-Baltic countries. RESULTS: Asthma and rhinitis are common conditions that are important in a public health perspective. There are gender differences in incidence and remission. A socio-economic gradient that non-atopic asthma is more strongly related to poverty seems to have developed in the last decade. These findings will challenge our welfare states in the future. In addition, occupational, as well as indoor and outdoor environmental exposures, influenced the onset of asthma. The population-attributable risk for adult asthma because of occupational exposures is equivalent to an incidence of new-onset asthma of 250-300 cases per million per year. Genetic factors, allergic sensitisation, gastro-oesophageal reflux, habitual snoring, diet and other factors may also contribute to the onset of asthma and rhinitis. Even though management of asthma has improved, there are still great variations throughout Europe. These findings highlight the key role doctors and nurses play in educating and reviewing management of patients.

Prevalence and incidence of respiratory symptoms in relation to indoor dampness: the RHINE study.

BACKGROUND: An association between indoor dampness and respiratory symptoms has been reported, but dampness as a risk factor for the onset or remission of respiratory symptoms and asthma is not well documented. METHOD: This follow up study included 16 190 subjects from Iceland, Norway, Sweden, Denmark, and Estonia who had participated in the European Community Respiratory Health Survey (ECRHS I). Eight years later the same subjects answered a postal questionnaire that included questions on respiratory symptoms and indicators of indoor dampness. RESULTS: Subjects living in damp housing (18%) had a significantly (p<0.001) higher prevalence of wheeze (19.1% v 26.0%), nocturnal breathlessness (4.4% v 8.4%), nocturnal cough (27.2% v 36.5%), productive cough (16.6% v 22.3%) and asthma (6.0% v 7.7%). These associations remained significant after adjusting for possible confounders. Indoor dampness was a risk factor for onset of respiratory symptoms but not for asthma onset in the longitudinal analysis (OR 1.13, 95% CI 0.92 to 1.40). Remission of nocturnal symptoms was less common in damp homes (OR 0.84, 95% CI 0.73 to 0.97). CONCLUSIONS: Subjects living in damp housing had a higher prevalence of respiratory symptoms and asthma. Onset of respiratory symptoms was more common and remission of nocturnal respiratory symptoms was less common in subjects living in damp housing.

Hormone replacement therapy, body mass index and asthma in perimenopausal women: a cross sectional survey.

BACKGROUND: Hormone replacement therapy (HRT) and obesity both appear to increase the risk of asthma. A study was undertaken to investigate the association of HRT with asthma and hay fever in a population of perimenopausal women, focusing on a possible interaction with body mass index (BMI). METHODS: A postal questionnaire was sent to population based samples in Denmark, Estonia, Iceland, Norway, and Sweden in 1999-2001, and 8588 women aged 25-54 years responded (77%). Pregnant women, women using oral contraceptives, and women <46 years were excluded. Analyses included 2206 women aged 46-54 years of which 884 were menopausal and 540 used HRT. Stratified analyses by BMI in tertiles were performed. RESULTS: HRT was associated with an increased risk for asthma (OR 1.57 (95% CI 1.07 to 2.30)), wheeze (OR 1.60 (95% CI 1.22 to 2.10)), and hay fever (OR 1.48 (95% CI 1.15 to 1.90)). The associations with asthma and wheeze were significantly stronger among women with BMI in the lower tertile (asthma OR 2.41 (95% CI 1.21 to 4.77); wheeze OR 2.04 (95% CI 1.23 to 3.36)) than in heavier women (asthma: p(interaction) = 0.030; wheeze: p(interaction) = 0.042). Increasing BMI was associated with more asthma (OR 1.08 (95% CI 1.05 to 1.12) per kg/m2). This effect was only found in women not taking HRT (OR 1.10 (95% CI 1.05 to 1.14) per kg/m2); no such association was detected in HRT users (OR 1.00 (95% CI 0.92 to 1.08) per kg/m2) (p(interaction) = 0.046). Menopause was not significantly associated with asthma, wheeze, or hay fever. CONCLUSIONS: In perimenopausal women there is an interaction between HRT and BMI in the effects on asthma. Lean women who were HRT users had as high a risk for asthma as overweight women not taking HRT. It is suggested that HRT and overweight increase the risk of asthma through partly common pathways.

Cheyne-Stokes respiration and supine dependency.

The influence of position during sleep on central apnoeas during Cheyne-Stokes respiration has not previously been studied systematically. The current authors aimed to study the effect of body position and sleep stages on central sleep apnoeas during Cheyne-Stokes respiration. A total of 20 consecutive patients with cardiovascular diseases and central sleep apnoea during Cheyne-Stokes respiration were investigated using nocturnal polysomnography, including a body position sensor mounted on the patient's sternum. The mean central apnoea-hypopnoea index was significantly higher in the supine position than in nonsupine positions (41+/-13 versus 26+/-12). The central apnoea-hypopnoea index was highest in sleep stages 1 and 2, and lowest in slow-wave sleep and rapid eye movement sleep. In every sleep stage, central apnoeas and hypopnoeas were more prevalent in the supine position compared with nonsupine positions. In conclusion, sleep in the supine body position increases the frequency of apnoeas and hypopnoeas in patients with Cheyne-Stokes respiration.

Snoring, sleep apnoea and swallowing dysfunction: a videoradiographic study.

OBJECTIVES: Snoring is associated with subclinical pharyngeal swallowing dysfunction, probably owing to vibration trauma to the pharyngeal tissues caused by snoring. Negative intrathoracic pressure during apnoea causes stretching of the velum and pharynx. The aim of this study was to investigate whether patients with severe sleep apnoea have an increased frequency of videoradiographically diagnosed subclinical pharyngeal swallowing dysfunction compared with snoring patients with or without mild sleep apnoea as well as with non-snoring controls. METHODS: Eighty consecutive patients referred for sleep apnoea recordings because of snoring were examined. Fourteen of these patients were excluded because they suffered from dysphagia. Fifteen non-snoring, non-dysphagic volunteers served as controls. Videoradiography was performed to examine the oral and pharyngeal swallowing function in patients and controls. Overnight sleep apnoea recordings were used to evaluate the apnoea-hypopnoea index (AHI). RESULTS: Pharyngeal swallowing dysfunction was observed in 34/66 (52%) of the snoring patients and in 1/15 (7%) of the non-snoring controls. Pharyngeal swallowing dysfunction was observed in 50% of patients with an AHI of >or=30, in 61% of patients with an AHI of 5-29 and in 43% of patients with an AHI of <5. There was no significant difference in the frequency of pharyngeal swallowing dysfunction between snoring patients with different AHIs. CONCLUSION: Snoring patients run an increased risk of developing subclinical pharyngeal swallowing dysfunction independent of concomitant sleep apnoea.

Sleep-disordered breathing and coronary artery disease: long-term prognosis.

The evidence linking sleep-disordered breathing to increased mortality and cardiovascular morbidity has been conflicting and inconclusive. We hypothesized that a potential adverse effect of disordered breathing would be more obvious in patients with established vascular disease. In a prospective cohort study 408 patients aged 70 yr or younger with verified coronary disease were followed for a median period of 5.1 yr. An apnea-hypopnea index (AHI) of > or = 10 and an oxygen desaturation index (ODI) of > or = 5 were used as the diagnostic criteria for sleep-disordered breathing. The primary end point was a composite of death, cerebrovascular events, and myocardial infarction. There was a 70% relative increase and a 10.7% absolute increase in the primary composite end point in patients with disordered breathing defined as an ODI of > or = 5 (risk ratio 1.70, 95% confidence interval [CI] 1.15-2.52, p = 0.008). Similarly, patients with an AHI of > or = 10 had a 62% relative increase and a 10.1% absolute increase in the composite endpoint (risk ratio 1.62, 95% CI 1.09-2.41, p = 0.017). An ODI of > or = 5 and an AHI of > or = 10 were both independently associated with cerebrovascular events (hazard ratio 2.62, 95% CI 1.26-5.46, p = 0.01, and hazard ratio 2.98, 95% CI 1.43-6.20, p = 0.004, respectively). We conclude that sleep-disordered breathing in patients with coronary artery disease is associated with a worse long-term prognosis and has an independent association with cerebrovascular events.

Nasal continuous positive airway pressure in stroke patients with sleep apnoea: a randomized treatment study.

The authors have investigated whether treatment of sleep apnoea with nasal continuous positive airway pressure (nCPAP) improves depressive symptoms, personal activities of daily living (ADL), cognitive functioning and delirium in patients that have suffered a stroke. Sixty-three patients consecutively admitted to a stroke rehabilitation unit 2-4 weeks after a stroke, with an apnoea/hypopnoea index > or =15, were randomized to either nCPAP treatment (n=33) or a control group (n=30). Four patients dropped out after randomization. Both groups were assessed at baseline and after 7 and 28 nights using the Montgomery-Asberg Depression Rating Scale (MADRS), Barthel-ADL index, and the Mini-Mental State Examination (MMSE) scale. Compared to the control group, depressive symptoms (MADRS total score) improved in patients randomized to nCPAP treatment (p=0.004). No significant treatment effect was found with regard to delirium, MMSE or Barthel-ADL index. Delirium and low cognitive level (MMSE score) explained poor compliance with nCPAP. Depressive symptoms are reduced through nasal continuous positive airway pressure treatment in patients with severe stroke and sleep apnoea. Compliance with nasal continuous positive airway pressure treatment is a problem in stroke patients, especially when delirium and severe cognitive impairment occur.

Mandibular advancement device in patients with obstructive sleep apnea : long-term effects on apnea and sleep.

STUDY OBJECTIVES: To evaluate the long-term effects on apneas and sleep and the tolerability of a mandibular advancement device in patients with obstructive sleep apnea. DESIGN: Prospective study. SETTING: Department of Respiratory Medicine, University Hospital, Umeå, Sweden. PATIENTS: Thirty-three consecutively treated patients. INTERVENTIONS: Individually adjusted mandibular advancement devices. MEASUREMENTS AND RESULTS: Polysomnographic sleep recordings on 1 night without the device and 1 night with the device were performed after 0.7 +/- 0.5 years (mean +/- SD) and after 5.2 +/- 0.4 years from the start of treatment. Nineteen of the 33 patients experienced a short-term satisfactory treatment result with an apnea-hypopnea index of < 10 events per hour and a satisfactory reduction in snoring. Fourteen patients were regarded as being insufficiently treated with the device. Seventeen of the short-term satisfactorily treated patients (90%) and 2 of the remaining patients continued treatment on a long-term basis. The apnea-hypopnea index was reduced by the device from 22 +/- 17 to 4.9 +/- 5.1 events per hour (p < 0.001) in these 19 long-term treatment patients, which did not differ from what was found at the short-term follow-up visits in these patients. Patients with their devices replaced or adjusted experienced a better long-term effect than patients still using their original devices (p < 0.05). CONCLUSIONS: The long-term effect and tolerability of a mandibular advancement device are good in patients who are recommended the treatment on the basis of a short-term sleep recording, provided that the device is continuously adjusted or replaced with a new one when needed. A short-term follow-up is valuable in the selection of patients who will benefit from long-term treatment with a mandibular advancement device.

Symptoms related to obstructive sleep apnoea are common in subjects with asthma, chronic bronchitis and rhinitis in a general population.

The purpose of this study was to examine the prevalence of self-reported snoring, apnoeas and daytime sleepiness in relation to chronic bronchitis, recurrent wheeze, physician-diagnosed asthma and rhinitis. This was a questionnaire study in a representative sample of a general population. The study was a part of the Obstructive Lung Disease in Northern Sweden Studies (OLIN). A total of 5424 subjects aged 20-69 years, born on the 15th day of each month, participated in the study. Eligible answers were obtained from 4648 subjects (85.7%). Having snoring as a problem was reported by 10.7%. Among subjects with chronic bronchitis it was reported by 25.9%, with recurrent wheeze by 21.3%, with physician-diagnosed asthma by 17.9%, and with rhinitis by 14.7%. Relatives' concerns of witnessed apnoea was reported by 6.8% of all subjects, while among subjects with chronic bronchitis it was reported by 18.1%, with recurrent wheeze by 17.1%, with physician-diagnosed asthma by 14.3%, and with rhinitis by 9.1%. After correction for age, gender and smoking habits, chronic bronchitis, rhinitis, asthma, and current smoking were significantly related, with snoring as a problem and with relatives' concern of witnessed apnoeas. Symptoms of daytime sleepiness were significantly related with concern of witnessed apnoeas, chronic bronchitis, snoring as a problem, recurrent wheeze and age 50-59 years. In conclusion, respiratory symptoms and conditions affecting mainly the lower respiratory tract, such as chronic bronchitis and asthma, were related with symptoms common in obstructive sleep apnoea.

Orthodontic side-effects of mandibular advancement devices during treatment of snoring and sleep apnoea.

The aims of this study were to investigate possible orthodontic side-effects following the use of mandibular advancement devices (MAD) in adults with snoring and sleep apnoea. A second objective was to analyse the effect of the appliance design. Seventy-five patients treated with MAD and 17 reference patients were studied at follow-up after 2.5 +/- 0.5 years. In the test group, 47 patients were provided with soft elastomeric devices, while the remaining 28 patients received hard acrylic devices. The treatment induced a change in overjet of -0.4 +/- 0.8 mm (mean +/- SD) and a change in overbite of -0.4 +/- 0.7 mm (mean +/- SD). These changes were larger than those found in the reference group (P < 0.01). The odds ratio (OR) for the largest quartile of reduction in overjet was 3.8 in patients using hard acrylic devices compared with those using soft elastomeric devices (P < 0.05). A large reduction in overjet in patients using the hard acrylic devices was unrelated to the degree of mandibular protrusion by the device. The OR for a large reduction in overjet in patients using the soft elastomeric devices with a protrusion of 6 mm or above was 6.8 compared with smaller mandibular protrusions (P < 0.05). The results indicate that the orthodontic side-effects are small during the treatment of adult subjects with MAD for snoring and sleep apnoea, especially in patients using soft elastomeric devices with mandibular protrusions of less than 6 mm. The follow-up of patients treated with MAD is recommended, as individual patients may experience marked orthodontic side-effects.