Late-onset central hypoventilation syndrome: a family genetic study.

Congenital central hypoventilation syndrome is a rare disorder characterised by chronic alveolar hypoventilation, which becomes more pronounced during sleep and may be associated with neurocristopathies, such as Hirchsprung's disease. A mutation in the PHOX2B gene has recently been identified. In a family of both parents and five offspring, detailed clinical assessment, pulmonary function testing, overnight sleep studies and ventilatory responsiveness to progressive hypercapnia (V'(R,CO(2))) were performed, in addition to analysis of known genetic loci for this condition. The father and four of the offspring demonstrated features of central hypoventilation with nonapnoeic oxygen desaturation during sleep and diminished V'(R,CO(2)), despite normal pulmonary function. The lowest sleep saturation was median (range) 79% (67-83%) and V'(R,CO(2)) was 2.1 (0.03-4.3) L x min(-1) x kPa(-1). The normal values for the authors' centre (St Vincent's University Hospital, Dublin, Ireland) are 15-40 L x min(-1) x kPa(-1). An in-frame five amino acid polyalanine expansion of the PHOX2B gene was found in all affected subjects, while the mother and fifth child, who did not have features of central hypoventilation, had a normal PHOX2B gene. Magnetic resonance imaging of the brainstem in one severely affected child was normal. The present study of a unique family confirms that transmission of late-onset congenital central hypoventilation syndrome is autosomal dominant in nature.

Reducing waiting times for sleep apnoea hypopnoea syndrome and snoring using a questionnaire and home oximetry: results of a second audit cycle.

As a result of a previous audit on the management of sleep apnoea hypopnoea syndrome (SAHS) which showed long waiting times that were primarily due to unnecessary interspecialty referrals, a change in practice was adopted. All referrals are now sent a questionnaire about symptoms suggestive of SAHS, the Epworth Sleepiness Scale score and their body mass index (BMI) which when returned are categorized into having a high, intermediate or low risk of SAHS. Those patients with a high probability have home overnight oximetry and those with intermediate probability have video oximetry. Those with a low probability are referred directly to ENT. We audited the first 100 patients referred. All were General Practitioner referrals to either ENT or respiratory medicine. Only two patients had a low probability score and were seen directly in ENT. Following sleep study analysis, 10 patients were referred directly to ENT with no respiratory medicine follow-up and nine were discharged back to the General Practitioner with no apnoea or snoring. Eighty-one patients were followed up by respiratory medicine. Of these, 49 received a trial of nasal continuous positive airway pressure (nCPAP) and six were referred to ENT. Therefore the majority justified an investigation to exclude SAHS in the first instance and an unnecessary initial ENT appointment was avoided. We have reduced the average waiting times to sleep study by approximately 90 days and to nCPAP trial by 32 days, mostly due to decreased delays in interspeciality referrrals. We have also demonstrated a greater than 50 per cent reduction in ENT clinic visits, a small increase in the number of sleep studies but no increase in respiratory clinic workload.

Prospective audit of a respiratory sleep disorders service at District General Hospital level.

This study was designed to examine the organisation and outcomes of a District General Hospital respiratory sleep service, since data are lacking on the management of sleep-disordered breathing at this level. Questionnaires and case-notes review were used to assess the management of 119 consecutive patients referred with suspected sleep-disordered breathing. Patients diagnosed with sleep-disordered breathing were assigned nasal continuous positive airway pressure (nCPAP), ear/nose/throat (ENT) surgery or simple measures (e.g., weight loss). There were six non-attenders. At 12 months follow-up, 33 patients had been assigned to nCPAP, 25 to ENT surgery, and 37 to simple measures. Of the remainder, nine had alternative diagnoses, two were still being assessed and seven were lost to follow-up. Patients prescribed nCPAP (81% compliance) had significant symptomatic improvements with low dissatisfaction rates (20%); patients on simple measures did not improve (33% dissatisfied); only half assigned surgery had it performed, with 42% awaiting surgery and dissatisfied. Interspecialty referral resulted in major delays (mean 16 weeks). Referral letters were generally unhelpful in deciding on the appropriateness of initial referral (respiratory physician vs ENT). nCPAP was generally effective in improving symptoms, with a high level of patient satisfaction, while simple measures did not improve symptoms and were associated with lower satisfaction levels. Waiting times to ENT surgery can be long and patients express significant dissatisfaction. Referral letters are not useful in directing initial referral. Services should be co-ordinated between respiratory and ENT specialties to reduce waiting times and improve patient satisfaction.

How do general practitioners respond to reports of abnormal chest X-rays?

General practitioners (GPs) in the UK have long had direct access to hospital radiological services, which in theory shortens investigation time and improves the quality of service. Chest X-rays (CXRs) account for a substantial proportion of requests, and we investigated what happened when an abnormality was detected. In one year, 204 GPs in the Nottingham area requested CXRs in 605 patients. 362 were reported normal, 165 abnormal but hospital follow-up not indicated and 71 abnormal with radiological follow-up or hospital referral indicated (mass lesion suspicious of tumours 27, infective shadowing 35, other 9). 64 of the 71 were seen in hospital within three months, and in those with suspected cancer the median time to follow-up was 20 days. These results show that GPs do act on the results of abnormal CXRs, but only 37% of those with a mass suspicious of cancer were seen in hospital within two weeks as recommended by the British Thoracic Society. Time might be saved if GPs agreed to direct referral from the radiology department to respiratory physicians.

Reducing waiting times in lung cancer.

BACKGROUND: Concern exists over delays in the management of lung cancer patients. Maximum waiting times and a multidisciplinary team (MDT) approach have been recommended in several recent national reports. OBJECTIVE: Having implemented a MDT approach, we wished to assess whether national recommendations were achievable and to identify the major factors causing delays. METHODS: Prospective survey over five months of all new referrals with suspected lung cancer, documenting waiting times at all stages from referral to definitive treatment. RESULTS: Of the total of 92 patients, 57 were outpatients (67% seen within one week, 89% within two weeks of receipt of referral) and 35 were inpatients (all seen within two working days). Patient age did not influence waiting times to first being seen or to investigation. The result of the initial diagnostic test was received within two weeks of first being seen in 86% of patients. All patients received definitive treatment within recommended times from diagnosis. Delays in the early part of the care pathway were largely due to potentially remediable service factors, but unavoidable patient related factors were important in some prolonged diagnostic delays. CONCLUSIONS: National recommendations on waiting times are achievable in a high proportion of cases. The probable importance of the MDT approach is discussed.

Resolution of obstructive sleep apnoea with growth in the Robin sequence.

A 12 year old female with the Robin sequence presented with a one year history of snoring, witnessed apnoeas and daytime sleepiness. Surgery in early childhood had consisted of cleft palate repair, tonsillectomy and adenoidectomy and, later, revision palatoplasty. Overnight polysomnography (PSG) demonstrated severe obstructive sleep apnoea syndrome with an apnoea/hypopnoea index (AHI) of 49 events x h(-1), and repetitive oxygen desaturations below 50%. Nasal continuous positive airway pressure (nCPAP) effectively controlled her sleep abnormalities. After 3 yrs of nCPAP therapy, she requested discontinuation and was fully reassessed. PSG without nCPAP revealed an AHI <5 events x h(-1) with no desaturations below 90% and normal sleep quality. A repeat lateral cephalometrogram showed increased mandibular length and posterior airway space and reduced soft palate length. The patient remains asymptomatic 9 months following nCPAP discontinuation. This case indicates that nasal continuous positive airway pressure is an effective nonsurgical therapy in children with obstructive sleep apnoea syndrome and the Robin sequence. It is likely that mandibular growth, increase in mandibular length and enlargement of the posterior airway space was responsible for the resolution of obstructive sleep apnoea syndrome in this case.

Goitre: a cause of obstructive sleep apnoea in euthyroid patients.

While hypothyroidism is considered to predispose to obstructive sleep apnoea (OSA), the presence of a goitre itself is not a recognized cause of OSA. We present the cases of two euthyroid patients with large goitres and clinical evidence of OSA, whose OSA symptoms significantly improved following partial thyroidectomy. This finding suggests that the goitre contributed to their symptoms.

Effects of positive airway pressure on upper airway dilator muscle activity and ventilatory timing.

To determine upper airway (UA) and ventilatory responses to nasal continuous positive airway pressure (CPAP) and expiratory positive airway pressure (EPAP), we quantitated changes in alae nasi (AN) and genioglossus (GG) electromyographic (EMG) activity, ventilatory timing, and end-expiratory lung volume (EELV) at various levels of CPAP and EPAP in six normal subjects during wakefulness and in seven during sleep. The same measurements were also made before and after UA anesthesia in six normal subjects during wakefulness. During both wakefulness and sleep, CPAP application significantly increased EELV and decreased AN and GG EMG activities. In contrast, EPAP significantly increased EMG activities of both muscles while also increasing EELV during wakefulness. The EMG responses were less marked during sleep. Anesthesia of the UA abolished the EMG responses to CPAP but not to EPAP. These results suggest that, in normal subjects, CPAP application causes a reflex reduction in UA dilator muscle activity mediated by UA sensory receptors. In contrast, EPAP increases UA dilator muscle activity, with the response mediated by conscious influences or reflexes arising outside of the UA.

Predictive value of clinical features for the obstructive sleep apnoea syndrome.

The advantage of being a National Referral Centre for patients with suspected obstructive sleep apnoea (OSA) was used to seek clinical factors predictive of OSA, and thus determine if the number of polysomnography tests required could be reduced. Patients were mainly primary referrals, from an island population of 3.5 million. Two hundred and fifty consecutive patients underwent clinical assessment, full polysomnography, and a detailed self-administered questionnaire. This represents one of the largest European studies, so far, utilizing full polysomnography. Fifty four percent (n = 134) had polysomnographic evidence of OSA (apnoea/hypopnoea index (AHI) > or = 15 events.h-1 sleep). Patients with OSA were more likely to be male, and had a significantly greater prevalence of habitual snoring, sleeping supine, wakening with heartburn, and dozing whilst driving. Alcohol intake, age and body mass index (BMI) were significant independent correlates of AHI. After controlling for BMI and age, waist circumference correlated more closely with AHI than neck circumference among males, while the opposite was true among females. No single factor was usefully predictive of obstructive sleep apnoea. However, combining clinical features and oximetry data, where appropriate, approximately one third of patients could be confidently designated as having obstructive sleep apnoea or not. The remaining two thirds of patients would still require more detailed sleep studies, such as full polysomnography, to reach a confident diagnosis.

Pathophysiology of obstructive sleep apnoea.

The pathophysiology of obstructive sleep apnoea (OSA) is complex and incompletely understood. A narrowed upper airway is very common among OSA patients, and is usually in adults due to nonspecific factors such as fat deposition in the neck, or abnormal bony morphology of the upper airway. Functional impairment of the upper airway dilating muscles is particularly important in the development of OSA, and patients have a reduction both in tonic and phasic contraction of these muscles during sleep when compared to normals. A variety of defective respiratory control mechanisms are found in OSA, including impaired chemical drive, defective inspiratory load responses, and abnormal upper airway protective reflexes. These defects may play an important role in the abnormal upper airway muscle responses found among patients with OSA. Local upper airway reflexes mediated by surface receptors sensitive to intrapharyngeal pressure changes appear to be important in this respect. Arousal plays an important role in the termination of each apnoea, but may also contribute to the development of further apnoea, because of reduction in respiratory drive related to the hypocapnia which results from postapnoeic hyperventilation. A cyclical pattern of repetitive obstructive apnoeas may result. A better understanding of the integrated pathophysiology of OSA should help in the development of new therapeutic techniques.

Topical oropharyngeal anesthesia in patients with obstructive sleep apnea.

Topical oropharyngeal anesthesia (TOPA) increases obstructive sleep apnea (OSA) frequency in both normal subjects and loud snorers. The effects of TOPA in established OSA were assessed in six male patients with a mean age (+/- SEM) of 50 +/- 5.3 yr. Following an acclimatization night, each subject underwent two overnight sleep studies, randomly assigned to TOPA (10% lidocaine spray and 0.25% bupivocaine gargle) and control (C) (saline placebo). Patients demonstrated sleep efficiencies of 93 +/- 2.9% (mean +/- SEM) during C and 88 +/- 2.9% during TOPA. Overall apnea-hypopnea (AH) frequency, using inductance plethysmography, showed little change: 21.2 +/- 3.6 on C versus 25.1 +/- 3.5 events/h on TOPA nights (p = 0.12). There was no significant increase in AH duration with TOPA, and oxygen desaturation (> or = 4%) frequency was similar: 21.1 +/- 3.9 per hour during TOPA versus 23.6 +/- 5.9 during C. However, obstructive AHs showed a change in thoracoabdominal motion from C to TOPA nights, with an increase in events with abdominal paradox from 3.1 +/- 1.1 to 10.3 +/- 3.1 per hour (p = 0.03), and a reduction in events with ribcage paradox from 13.1 +/- 1.6 to 8.2 +/- 2.4 per hour (p = 0.08). Central and mixed AHs demonstrated similar frequencies on both nights. These data support an impairment of upper airway (UA) protective reflexes among patients with OSA.

Treatment of Robin sequence with nasal CPAP.

A 12-year-old schoolgirl presented with severe obstructive sleep apnoea due to the Robin sequence. The sleep apnoea, together with the associated findings of daytime sleepiness, nocturia, right heart strain and growth retardation, were successfully reversed by nasal CPAP therapy. This therapy allows postponement of a decision concerning corrective surgery until after full growth has occurred.

Haemodynamic effects of nasal continuous positive airway pressure in severe congestive heart failure.

Nasal continuous positive airway pressure (NCPAP) during sleep may be a useful adjunct to medical therapy in patients with stable severe congestive heart failure (CHF), particularly when there is a coexisting respiratory sleep disorder. However, the direct haemodynamic effects of NCPAP in patients with severe stable CHF have not yet been adequately assessed. Right heart catheter studies were performed in seven awake males (aged 51-75 yrs) with stable CHF, before, during and after the application of 5 cmH2O NCPAP over 3 h. All patients had left ventricular ejection fractions < or = 30% and baseline pulmonary capillary wedge pressures > 12 mmHg, and six patients were in atrial fibrillation. Cardiac index fell from baseline in all patients whilst on NCPAP, with the greatest fall at 2 h (from 3.3 +/- 0.3 (mean +/- SEM) at baseline to 2.8 +/- 0.2 l.min-1.m-2) and rose back to baseline after NCPAP withdrawal. Systemic vascular resistance (SVR) increased during NCPAP application (1,268 +/- 108 to 1,560 +/- 82 dyn.s-1.cm5), with baseline SVR showing a significant negative correlation vs percentage fall in cardiac index (CI) at 2 h on multiple linear regression analysis (r2 = 0.8). These data indicate that domiciliary nocturnal NCPAP should not be prescribed as part of the therapy in severe CHF without first determining the individual patient's cardiac response to such therapy.

Continuous non-invasive monitoring of evolving acute severe asthma during sleep.

A spontaneous acute severe asthmatic attack was monitored non-invasively in a 27 year old sleeping female asthmatic subject. As the attack evolved there was a switch from predominant abdominal breathing (associated with inspiratory indrawing of the rib cage) to gradually increasing rib cage excursion (associated with inspiratory paradox of the abdominal wall with respect to the rib cage). Abdominal paradox increased progressively until it appeared to fill the whole of the inspiratory period of the rib cage, at which point rapid oxygen desaturation developed.

Role of respiratory sleep disorders in the pathogenesis of nocturnal angina and arrhythmias.

This report documents how respiratory sleep disorders can adversely effect ischaemic heart disease. Three male patients (aged 60-67 years) with proven ischaemic heart disease are described. They illustrate a spectrum of nocturnal cardiac dysfunction, two with nocturnal angina and one with nocturnal arrhythmias. Full sleep studies were performed in a dedicated sleep laboratory on all patients, and one patient had 48 hours of continuous Holter monitoring. Two patients were found to have obstructive sleep apnoea with apnoea/hypopnoea indices of 57 and 36 per hour, respectively, the former with nocturnal arrhythmias and the latter with nocturnal angina. In both cases, nasal continuous positive airways pressure successfully treated the sleep apnoea, with an associated improvement in nocturnal arrhythmias and angina. The third patient who presented with nocturnal angina, did not demonstrate obstructive sleep apnoea (apnoea/hypopnoea index = 7.2) but had significant oxygen desaturation during rapid eye movement (REM) sleep. This patient responded to a combination of nocturnal oxygen and protriptyline, an agent known to suppress REM sleep, and had no further nocturnal angina. All patients were considered to be an optimum cardiac medication and successful symptom resolution only occurred with the addition of specific therapy aimed at their sleep-related respiratory problem. We conclude that all patients with nocturnal angina or arrhythmias should have respiratory sleep abnormalities considered in their assessment.