Serial lung function tests in primary immune deficiency.

Pulmonary complications are common in patients with primary immune deficiency (PID). The aim of this study was to assess the usefulness of lung function tests (LFTs) in the management of these patients, and in particular to see if carbon monoxide transfer factor (TLCO) is needed in addition to spirometry. We studied 20 patients (11 female) with PID in a tertiary referral clinic, with a mean age of 47.6 years. Serial LFTs, spanning a mean of 101 months, were correlated with immunoglobulin levels and antibiotic usage. Seven patients showed a decline in forced expiratory volume in 1 second over the period of the study. An additional five patients showed a decline in TLCO. Of these 12 patients, two had no radiographic evidence of lung disease. Higher levels of immunoglobulin were associated with slower decline in LFTs (P < 0.05). The analysis of antibiotic usage and LFTs failed to show a statistically significant effect, although there was a trend towards a slower rate of decline with greater use of antibiotics. LFTs decline slowly in patients with PID. Annual testing (both spirometry and transfer factor) is useful in the assessment of these patients, and should not be confined to those with radiological evidence of lung disease.

Respiratory involvement in inherited primary muscle conditions.

Patients with inherited muscle disorders can develop respiratory muscle weakness leading to ventilatory failure. Predicting the extent of respiratory involvement in the different types of inherited muscle disorders is important, as it allows clinicians to impart prognostic information and offers an opportunity for early interventional management strategies. The approach to respiratory assessment in patients with muscle disorders, the current knowledge of respiratory impairment in different muscle disorders and advice on the management of respiratory complications are summarised.

Tubular aggregate myopathy presenting with acute type II respiratory failure and severe orthopnoea.

Acute hypercapnic respiratory failure (AHRF) is a common reason for hospital admission. Most patients have an underlying chronic lung disease such as chronic obstructive pulmonary disease. We report the case of a man who presented with AHRF secondary to tubular aggregate myopathy.

Trends in survival from muscular dystrophy in England and Wales and impact on respiratory services.

Respiratory failure is an important terminal event in muscular dystrophy, but increasingly is effectively treated by non-invasive ventilation. This study was designed to assess mortality statistics in this patient group in order to get an indication of future demand. Mortality data for all deaths from muscular dystrophy registered by death certification in England and Wales between 1993 and 1999 were analysed. In total, 817 deaths from muscular dystrophy were registered between 1993 and 1999. Annual number of deaths was unchanged over this period. Median age at death (interquartile range) for all cause muscular dystrophy increased from 20 (17-42.5) years in 1993, to 26 (17.5-63) years in 1999. Respiratory failure was the primary or contributory cause of death in 82% of cases. Two thirds of these deaths were during acute infection. We can expect 100 patients with muscular dystrophy to develop respiratory failure in England and Wales each year, so non-invasive ventilation services probably need to be able to provide for 0.2 new patients per 100,000 population annually. Respiratory services also need to provide adequate monitoring and early treatment of infection in these patients.

The effect of a mechanical glottis on peak expiratory flow rate and time to peak flow during a peak expiratory flow manoeuvre: a study in normal subjects and patients with motor neurone disease.

We have evaluated a mechanical glottis in healthy volunteers and in patients with bulbar motor neurone disease. In healthy volunteers, the mechanical glottis increased peak flow rate and decreased the time to peak flow during forced expiration, but cough produced even higher flow rates and shorter times to peak flow. In patients, the mechanical glottis increased peak flow rate and decreased the time to peak flow. The mechanical glottis also produced higher peak flow rates when compared to the cough manoeuvres, and the time to peak flow was also significantly shorter with the mechanical glottis. We have shown that the use of a mechanical glottis tends to convert the airflow profile of a peak expiratory flow manoeuvre into that of a cough in both healthy volunteers and patients with motor neurone disease. Its potential role as an aid to clearance of airway secretions in patients with impaired laryngeal function remains to be seen.

Patterns of mortality in patients with motor neurone disease.

OBJECTIVE: Motor neurone disease (MND) is a rapidly fatal condition with survival of less than 4 years. Patients can deteriorate quickly in the preterminal stages resulting in inappropriate resuscitation or admission to intensive care units (ICU) or accident and emergency (A & E). MATERIAL AND METHODS: We looked at patterns of mortality with emphasis on the place of death. A retrospective study was performed of all patients attending an MND clinic, who had died within a 10-year period. RESULTS: Of 179 patients (63 female), 81 patients (45%) died at home, in a hospice or in a nursing home. Sixty-five patients (36%) died in hospital (11 in ICU or A & E). Nine of the latter were previously known to have MND and six admissions were probably avoidable. Most ward patients died of respiratory causes and were treated conservatively. CONCLUSION: The proportion of patients dying in A & E or ICU was small but could have been reduced further. A number of those who died on the wards could probably have been managed conservatively at home. Older patients and those with bulbar disease had a poorer prognosis.

Relationship between supramaximal flow during cough and mortality in motor neurone disease.

The main function of cough is clearance of intrathoracic airways. A normal cough is characterized by a transient increase in expiratory flow above the maximal flow-volume loop envelope, known as cough "spikes". They may be absent in patients with motor neurone disease. The relationship between cough pattern, pulmonary function and survival was studied. Fifty-three patients were recruited (25 bulbar). Vital capacity, maximal inspiratory and expiratory mouth pressures and cough flow/volume curves were performed on all patients, and the presence or absence of spikes were recorded. The primary endpoints were mortality or initiation of ventilatory support over a period of 18 months. Thirty-five patients died over the 18-month period of the study (including the six who were started on noninvasive ventilation). Twelve of the 24 patients with spikes died compared to 23 out of 29 patients without spikes (p<0.05). Patients without spikes were more likely to be bulbar on clinical grounds (p<0.0001) and had poorer lung function. The results showed an association between the absence of cough spikes and increased mortality. However the main determinants of survival in motor neurone disease are age, vital capacity and inspiratory mouth pressure, and it remains to be shown whether regular monitoring of cough conveys any additional advantage.

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.

Cognitive impairment in heart failure with Cheyne-Stokes respiration.

OBJECTIVES: To document the degree of cognitive impairment in stable heart failure, and to determine its relation to the presence of Cheyne-Stokes respiration during sleep. SUBJECTS: 104 heart failure patients and 21 healthy normal volunteers. METHODS: Overnight oximetry was used (previously validated as a screening tool for Cheyne-Stokes respiration in heart failure). Cognitive function was assessed using a battery of neuropsychological tests. Left ventricular function was assessed by echocardiography. RESULTS: Heart failure patients performed worse than the healthy volunteers in tests that measured vigilance. Reaction times were 48% slower (0.89 (0.03) s v 0.60 (0.05) s p < 0.005) and they hit twice as many obstacles on the Steer Clear simulator (75 (6.4) v 33 (4.6); p < 0.005). Cognitive impairment within the heart failure group was unrelated to either the presence of Cheyne-Stokes respiration, the degree of left ventricular dysfunction, or indices of nocturnal oxygenation. CONCLUSIONS: Vigilance was impaired in heart failure but this did not appear to be related to the presence of Cheyne-Stokes respiration during sleep. Impaired vigilance as measured on the Steer Clear test has been associated with an increased risk of motor vehicle accidents. The issue of fitness to drive in heart failure requires further attention.

Sniff nasal inspiratory pressure as a marker of respiratory function in motor neuron disease.

Vital capacity (VC) and maximum mouth pressures are often used to monitor respiratory function in motor neuron disease (MND), but require the use of a mouthpiece. Sniff nasal inspiratory pressure (SNIP) is a simple and reliable means of measuring inspiratory muscle strength; it does not involve the use of a mouthpiece and might therefore be better than VC or mouth pressures for assessing patients with bulbar disease. SNIP, maximum inspiratory (MIP) and expiratory mouth pressure (MEP), VC and arterial carbon dioxide tension (Pa,CO2) were measured in 59 consecutive patients attending a specialist MND clinic. Thirty-one had bulbar involvement on clinical grounds. Both SNIP and VC were inversely related to Pa,CO2 in nonbulbar patients only. Neither MIP nor MEP were related to Pa,CO2. The 10 patients with an elevated Pa,CO2 (>6 kPa) had significantly lower SNIP and VC than normocapnic patients. Sniff nasal inspiratory pressure can be used to monitor respiratory function in motor neuron disease. It is quick and easy for patients to perform, but otherwise appears to offer little advantage over vital capacity measurement. Patients with bulbar disease are often poor at performing sniff nasal inspiratory pressure manoeuvres, possibly because of upper airway collapse or inability to close the mouth completely during the manoeuvre.

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.

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.

A randomized controlled trial of inspiratory muscle training in stable chronic heart failure.

AIMS: To assess whether a domiciliary programme of specific inspiratory muscle training in stable chronic heart failure results in improvements in exercise tolerance or quality of life. METHODS AND RESULTS: We conducted a randomized controlled trial of 8 weeks of inspiratory muscle training in 18 patients with stable chronic heart failure, using the Threshold trainer. Patients were randomized either to a training group inspiring for 30 min daily at 30% of maximum inspiratory mouth pressure, or to a control group of 'sham' training at 15% of maximum inspiratory mouth pressure. Sixteen of the 18 patients completed the study. Maximum inspiratory mouth pressure improved significantly in the training group compared with controls, by a mean (SD) of 25.4 (11.2) cmH2O (P=0.04). There were, however, no significant improvements in treadmill exercise time, corridor walk test time or quality of life scores in the trained group compared with controls. CONCLUSION: Despite achieving a significant increase in inspiratory muscle strength, this trial of simple domiciliary inspiratory muscle training using threshold loading at 30% of maximum inspiratory mouth pressure did not result in significant improvements in exercise tolerance or quality of life in patients with chronic heart failure.

Effect of oxygen on sleep quality, cognitive function and sympathetic activity in patients with chronic heart failure and Cheyne-Stokes respiration.

BACKGROUND: Cheyne-Stokes respiration disrupts sleep, leading to daytime somnolence and cognitive impairment. It is also an independent marker of increased mortality in heart failure. This study evaluated the effectiveness of oxygen therapy for Cheyne-Stokes respiration in heart failure. METHODS: Eleven patients with stable heart failure and Cheyne-Stokes breathing were studies. Oxygen and air were administered for 4 weeks in a double-blind, cross-over study. Sleep and disordered breathing was assessed by polysomnography. Symptoms were assessed using the Epworth Sleepiness Scale, visual analogue and quality of lift scores. Cognitive function was assessed by neuropsychometric testing. Overnight urinary catecholamine excretion was used as a measure of sympathetic nerve activity. RESULTS: Ninety-seven percent of apnoeas were central in origin. Oxygen therapy reduced the central apnoea rate (18.4 +/- 4.1 vs 3.8 +/- 2.1 per hour; p = 0.05) and periodic breathing time (33.6 +/- 7.4 vs 10.7 +/- 3.9% of actual sleep time; p = 0.003). Oxygen did not improve sleep quality, patient symptoms or cognitive failure. Oxygen reduced urinary noradrenaline excretion (8.3 +/- 1.5 vs 4.1 +/- 0.6 nmol.mmol-1 urinary creatinine; p = 0.03). CONCLUSION: Oxygen stabilized sleep disordered breathing and reduced sympathetic activity in patients with heart failure and Cheyne-Stokes respiration. We were unable to demonstrate an effect on either patient symptoms or cognitive function.

Nocturnal desaturation in patients with stable heart failure.

OBJECTIVE: To determine the prevalence of sleep disordered breathing within a United Kingdom heart failure population. SUBJECTS: 104 patients and 21 matched normal volunteers. METHODS: Overnight home pulse oximetry with simultaneous ECG recording in the patient group; daytime sleepiness was assessed using the Epworth sleepiness scale (ESS); 41 patients underwent polysomnography to assess the validity of oximetry as a screening test for Cheyne-Stokes respiration. RESULTS: Home oximetry was a good screening test for Cheyne-Stokes respiration (specificity 81%, sensitivity 87%). Patients with poorer New York Heart Association (NYHA) classes had higher sleepiness scores (p < 0.005). Twenty three patients had "abnormal" patterns of nocturnal desaturation suggestive of Cheyne-Stokes respiration. The mean (SEM) frequency of dips in Sao2 exceeding 4% was 10.3 (0.9) per hour in the patients and 4.8 (0.6) in normal controls (p < 0.005). Ejection fraction correlated negatively with dip frequency (r = -0.5, p < 0.005). The patient subgroup with > or = 15 dips/hour had a higher mean (SEM) NYHA class (3.0 (0.2) v 2.3 (0.1), p < 0.05), and experienced more ventricular ectopy (220 (76) v 78 (21) beats/hour, p < 0.05). There was no excess of serious arrhythmia. CONCLUSIONS: Nocturnal desaturation is common in patients with treated heart failure. Low ejection fraction was related to dip frequency. Lack of correlation between dips and ESS suggests that arousal from sleep is more important than hypoxia in the aetiology of daytime sleepiness in heart failure. Overnight oximetry is a useful screening test for Cheyne-Stokes respiration in patients with known heart failure.

Incremental threshold loading: a standard protocol and establishment of a reference range in naive normal subjects.

Incremental threshold loading (ITL) has been proposed as a test of inspiratory muscle strength and endurance. To date, however, there has been no standardized protocol for an ITL test, and no reference range, with different investigators using a variety of different pressure increments in small numbers of subjects. We developed an ITL test using the weighted plunger (WP) principle, which uses standard increments of pressure. In our protocol subjects inspire through the WP generating an initial threshold opening pressure of 10 cmH2O. This pressure is raised at 2 min intervals in increments of 5 cmH2O until they fail to lift the plunger on two consecutive attempted breaths. Sixty healthy volunteers (30 males and 30 females) aged 20-80 yrs performed the ITL test. Twelve subjects (six females and six males) performed the test twice to assess reproducibility and repeatability. Using stepwise multiple linear regression, we regressed the maximum threshold pressure sustained for a full 2 min (Pmax) against age, height, weight and static maximum inspiratory mouth pressure (MIP). Pmax was significantly related to age but not to either height or weight, the regression equation for males was Pmax (cmH2O)=103.8 - (1.0 x age in years), and for females was Pmax (cmH2O)=93.7 - (1.0 x age in years). The within-subject standard deviation for those repeating the ITL test was 5.4 cmH2O. Incremental threshold loading is a simple technique with good reproducibility, which most naive subjects can use without difficulty. By using standard pressure increments and performing the test in a large number of naive subjects, we have established a reference range that should be applicable wherever similar pressure increments are used.