Pneumococcal serotyping and antigen detection in pneumococcal pneumonia of adults.

A retrospective study of 125 patients presenting to the City Hospital, Edinburgh, with proven pneumococcal pneumonia showed that pneumococcus serotype 3 remains the most prevalent and that since 1970 the distribution of serotypes has remained virtually constant. The frequency of diagnosing pneumococcal pneumonia is increased by the use of countercurrent immuno-electrophoresis (CIE) of sputum. In this series, 25 per cent of patients with negative sputum culture but radiological evidence of pneumonia, were diagnosed by means of this method, which was overall more helpful in making the diagnosis than blood cultures. All nine deaths in this series were in those over 65 years of age.

Sustained release choline theophyllinate in nocturnal asthma.

Nocturnal wheeze is common in patients with asthma, and slow release theophyllines may reduce symptoms. As theophyllines are stimulants of the central nervous system the effect of 10 days' twice daily treatment with sustained release choline theophyllinate or placebo on symptoms, overnight bronchoconstriction, nocturnal oxygen saturation, and quality of sleep were studied in a double blind crossover study in nine stable patients with nocturnal asthma (five men, four women, age range 23-64 years; forced expiratory volume in one second (FEV1) 0.85-3.8 1; vital capacity 1.95-6.1 1). When treated with the active drug all patients had plasma theophylline concentrations of at least 28 mmol/l (5 micrograms/ml) (peak plasma theophylline concentrations 50-144 mmol/l (9-26 micrograms/ml]. Morning FEV1 was higher when treated with sustained release choline theophyllinate (2.7 (SEM 0.3) 1) than placebo (2.1 (0.3) 1) (p less than 0.01). Both daytime and nocturnal symptoms were reduced when the patients were treated with sustained release choline theophyllinate and subjective quality of sleep was improved (p less than 0.002). When treated with the active drug, however, quality of sleep determined by electroencephalography deteriorated with an increase in wakefulness and drowsiness (p less than 0.05) and a reduction in non-rapid eye movement sleep (p less than 0.005). Treatment with choline theophyllinate had no effect on either the occurrence or the severity of transient nocturnal hypoxaemic episodes or apnoeas or hypopnoeas. In conclusion, sustained release choline theophyllinate prevents overnight bronchoconstriction, but impairs quality of sleep defined by electroencephalography.

Regional distribution of ventilation in chronic obstructive lung disease and the effect of salbutamol.

Regional distribution of ventilation was assessed in 5 normal volunteers, and 19 patients with symptomatic chronic obstructive lung disease (COAD) using the technique of gated lung ventilation imaging with 127Xe. The results of this technique were compared with the more conventional assessment of regional ventilation by analysis of 127Xe wash-out curves. Both techniques demonstrate loss of the normal gravitational distribution of ventilation in patients with severe COAD which is significantly reduced from normals in upper, middle and lower zones of each lung, being most marked in the lower zones (p less than 0.01). Gated lung imaging also shows a significant reduction of regional ventilation in patients with mild to moderate COAD compared to normals but only in the lower zones (p less than 0.05). Gated lung imaging provides a better quantitative method of assessing regional lung function than wash-out analysis and confirms loss of the normal gravitational distribution of ventilation in patients with obstructive lung disease and relates this to severity of disease. The distribution of ventilation was also assessed in 6 patients with severe COAD before and after placebo or salbutamol. There was a significant improvement of the distribution of ventilation to the lung bases after salbutamol (p less than 0.05).

Sodium cromoglycate in nocturnal asthma.

To investigate whether mast cell degranulation was important in producing nocturnal asthma, the effect of a single high dose of nebulised sodium cromoglycate on overnight bronchoconstriction, oxygen saturation, and breathing patterns in eight patients with nocturnal wheeze was examined. The study took the form of a double blind placebo controlled crossover comparison. Treatment with cromoglycate did not reduce the overnight fall in FEV1 or FVC, although it was associated with improved nocturnal oxygenation. This study suggests that mast cell degranulation may not be important in the pathogenesis of nocturnal asthma.

Breathing patterns during sleep in patients with nocturnal asthma.

Breathing patterns early and late in the night, at the same sleep stage, were compared in six healthy subjects and 15 adults with nocturnal asthma, to try to identify changes of overnight bronchoconstriction, and breathing patterns at different sleep stages, to see whether there were changes related to sleep stages that were indicative of bronchoconstriction. Despite an average 31% fall in FEV1 overnight in the patients with asthma, neither breathing frequency nor expiratory time, which might be expected to change during bronchoconstriction, was different early in the night from late in the night, nor did they differ between sleep stages. There was no evidence of asynchronous movement of the chest and abdomen in any patient. This study did not identify any abnormality of breathing pattern that would indicate the development of nocturnal asthma without the need to awaken the patient.

Do sleep studies contribute to the management of patients with severe chronic obstructive pulmonary disease?

To determine whether studies of breathing and oxygenation during sleep are clinically useful, we have assessed whether the detection of excess nocturnal hypoxemia in patients with chronic obstructive pulmonary disease (COPD) is of prognostic importance. Ninety-seven patients with COPD were followed for 32 to 108 (median, 70) months after studies of overnight oxygenation. Significant relationships (p less than 0.001) were obtained between mean oxygen saturation (SaO2) asleep and awake. There was similarly a significant relationship between lowest SaO2 asleep and awake, but this relationship was improved by the inclusion of awake arterial carbon dioxide tension (PaCO2). The patients who were more hypoxic at night than predicted from these regression relationships had similar survivals to the patients who were less hypoxic at night than predicted, whether excess nocturnal hypoxia was defined in terms of mean or lowest SaO2 during sleep. In the 66 patients who did not subsequently receive long-term oxygen therapy, none of the indices of nocturnal oxygenation was related to survival, the only significant predictor of survival being daytime arterial oxygen tension (PaO2). For all 97 patients, both mean nocturnal SaO2 and lowest SaO2 during sleep were related to survival (p less than 0.05), and percent predicted vital capacity was also related to survival (p less than 0.05). Neither of the oxygen saturations during sleep significantly added to the more readily and cheaply measured percent predicted vital capacity in determining survival in these patients. Thus, in patients with COPD, excess nocturnal hypoxemia is not associated with an impaired prognosis, and so studies of oxygenation during sleep cannot be recommended in the routine clinical management of these patients.

A comparison of the effects of almitrine or oxygen breathing on pulmonary arterial pressure and right ventricular ejection fraction in hypoxic chronic bronchitis and emphysema.

Almitrine bismesylate is a new, orally administered, respiratory stimulant that improves arterial blood gas tensions in patients with chronic bronchitis and emphysema, and it may have an effect on the pulmonary circulation and on right ventricular performance. We have, therefore, compared the effects of Almitrine with those of oxygen (given as 3 L/min by nasal prongs) on arterial blood gas tensions, mean pulmonary arterial pressure (Ppa), and right ventricular ejection fraction (RVEF) measured both at rest and during exercise in patients with chronic hypoxemia caused by chronic bronchitis and emphysema. Arterial oxygen tension improved significantly both at rest and during exercise after either 100 mg Almitrine by mouth or when breathing oxygen, both at rest and during exercise. Almitrine increased the mean Ppa at rest from 22 +/- 4 to 35 +/- 5 mmHg (p less than 0.001), and mean Ppa rose further during exercise from 38 +/- 5 mmHg before Almitrine to 49 +/- 7 mmHg (p less than 0.001) after Almitrine. In contrast, oxygen breathing did not change Ppa when at rest but reduced the amount of rise in Ppa during exercise. The change in Ppa after Almitrine correlated with the plasma Almitrine concentration (r = 0.69, p less than 0.05) and was associated with a fall in RVEF at rest from 0.38 +/- 0.03 to 0.32 +/- 0.02 (p less than 0.001). In 5 of the patients who received 50 mg of Almitrine by mouth twice daily for 3 months, the Ppa both at rest and during exercise remained significantly higher than in the control study before receiving Almitrine, but RVEF was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Nocturnal cough in patients with chronic bronchitis and emphysema.

Patients with respiratory disease commonly report that their sleep is disrupted by nocturnal cough. We have recorded cough during the night in 10 patients with severe chronic bronchitis and emphysema (forced expiratory volume in one second, 1.0 +/- SEM 0.1/L) who complained of nocturnal cough and correlated cough with electroencephalographic sleep stage and arterial oxygenation. Cough was recorded using a directional microphone and an auto-editing tape recorder system. Each cough was subsequently verified by a listener. There was a mean of 14.6 +/- 4.5 bouts of coughing per patient per night, each bout lasting on average 3.9 +/- 0.2 s. Eighty-five percent of coughing bouts occurred during electroencephalographically confirmed wakefulness (p less than 0.02 versus sleep), and coughs during true sleep were rare, with only 1 patient coughing during rapid eye movement sleep and none during Stages 3 and 4 sleep. Cough was only once followed by arousal. There was no correlation between cough and either apneas or hypoxemia during sleep. We conclude that spontaneous cough is suppressed during sleep and only rarely awakens patients.

C7 deficiency in an Irish family: a deletion defect which is predominant in the Irish.

Human deficiencies of terminal complement components are known to be associated with increased susceptibility to Neisseria meningitidis infection. Polymorphic DNA marker studies in complement deficient investigations allow identification of haplotypes associated with the deficiency and enable the possible identification of heterozygote carriers of the defect. We report studies of an Irish family in which the index case had suffered recurrent meningococcal disease and was found to be deficient in the seventh component of complement (C7). The availability of all family members enabled us to determine the segregating haplotypes. The defects in the family segregated with two very closely related C6 and C7 DNA haplotypes, one of which is known to be associated with the large Irish C7 DNA deletion defect. The index case and two C7 deficient siblings were found to be homozygous for this defect, a deletion that spans approx. 6.8 kbp and encompasses exons 7 and 8. The deletion defect of exons 7 and 8 of C7 has been found in homozygous form in another C7 deficient Irish individual, and is present in heterozygous form in C7 deficient members of a third Irish family. Therefore, this deletion defect occurs in five of the six deficient chromosomes of these three unrelated Irish families, raising the interesting question of how prevalent this defect may be within the Irish community.

Almitrine improves oxygenation when both awake and asleep in patients with hypoxia and carbon dioxide retention caused by chronic bronchitis and emphysema.

Patients with chronic bronchitis and emphysema who are hypoxic when awake become more hypoxic during sleep, with a further rise in their preexisting pulmonary hypertension. Almitrine, a respiratory stimulant, improves arterial blood gas tensions in such patients when they are awake. We have used a double-blind, placebo-controlled, cross-over study to compare the effects of 50 mg almitrine given orally twice a day for 14 days on oxygen saturation (SaO2), respiratory movements, and sleep quality in 9 patients with hypoxic chronic bronchitis and emphysema (FEV1, 0.4 to 1.0 L; PaO2, 51 +/- (SEM) 2 mmHg; PaCO2, 49 +/- 1 mmHg). Almitrine improved arterial blood gas tensions when awake, mean PaO2 rising by 8 mmHg (p less than 0.001) and PaCO2 falling by 4 mmHg (p less than 0.01). Almitrine improved nocturnal oxygenation, mean SaO2 when awake rising from 83 +/- 4% to 89 +/- 3% (p less than 0.01), and the lowest SaO2 during sleep rising on average from 65 +/- 6% to 77 +/- 3% (p less than 0.02). The number of hypoxemic episodes (SaO2 falling by greater than or equal to 10% from the preceding stable baseline during sleep) and the time when SaO2 was below 80% (135 +/- 53 versus 46 +/- 35 min; p less than 0.01) also improved. Almitrine did not improve sleep quality. We conclude that almitrine improves arterial gas tensions when awake and reduces the frequency and severity of nocturnal hypoxemia without impairing sleep quality in patients with chronic bronchitis and emphysema who are both hypoxemic and hypercapnic when awake.(ABSTRACT TRUNCATED AT 250 WORDS)