Damp housing and asthma: a case-control study.

BACKGROUND: Several epidemiological studies have reported a higher prevalence of respiratory symptoms in subjects living in damp housing, but links with specific respiratory diseases such as asthma have not been satisfactorily established. METHODS: One hundred and two subjects with physician diagnosed asthma and 196 age and sex matched controls were interviewed; 222 (75%) then agreed to have their dwelling surveyed for dampness. The prevalence of both self-reported and observed dampness in the homes of the asthmatic subjects and controls were compared. Both asthma and the severity of the dampness were quantified so that the possibility of a dose-response relationship could be investigated. RESULTS: Asthmatic subjects reported dampness in their current (odds ratio (OR) 1.92, 95% confidence interval (CI) 1.18 to 3.12) and previous (OR 2.11, 95% CI 1.29 to 3.47) dwellings more frequently than control subjects. The surveyor confirmed dampness in 58 of 90 (64%) dwellings of asthmatic subjects compared with 54 of 132 (41%) dwellings of control subjects (OR 2.62, 95% CI 1.50 to 4.55). This association persisted after controlling for socioeconomic and other confounding variables (adjusted OR 3.03, 95% CI 1.65 to 5.57). The severity of asthma was found to correlate statistically with measures of total dampness (r = 0.30, p = 0.006) and mould growth (r = 0.23, p = 0.035) in the dwelling. Patients living in homes with confirmed areas of dampness had greater evidence of airflow obstruction than those living in dry homes (mean difference in forced expiratory volume in one second (FEV1) 10.6%, 95% CI 1.0 to 20.3). CONCLUSIONS: Asthma is associated with living in damp housing and there appears to be a dose-response relationship. Action to improve damp housing conditions may therefore favourably influence asthma morbidity.

Generic inhaled salbutamol versus branded salbutamol. A randomised double-blind study.

Generic substitution of salbutamol lags behind that of other drugs in Scotland and a negative perception by both patients and doctors may explain this. The aim of this study was to assess whether, in clinical practice, there was any difference in efficacy between branded salbutamol (Ventolin) and a generic preparation. Asthmatic patients using a Ventolin metered-dose inhaler at least twice a day for symptom relief were entered into a double-blind cross-over study, comparing Ventolin, blinded Ventolin and a generic salbutamol in random order for two weeks each. Daily peak flows, inhaler use and bronchodilator response were recorded. At the end of each treatment period patients rated their inhaler against their usual Ventolin on a 5-point scale. Forty patients were entered into the study; 90% received 1000 micrograms or more of inhaled steroids per day. Eleven patients dropped out during the run-in phase. In the remaining 29 patients, no significant difference between treatments could be found in any of the objective parameters measured. Fifty-five per cent of patients said they could detect a difference between the inhalers, and 45% noted a difference between their usual Ventolin and the open or blinded Ventolin. This study showed clinical equivalence between a generic and branded salbutamol. Patients' own assessment of their relief inhaler seems to be influenced by factors other than efficacy. The study highlights that careful encouragement is required when changing to a generic product and has particular implications for the forthcoming conversion to CFC-free products.

Sedation for fibre optic bronchoscopy.

Most current sedative regimens for fibre optic bronchoscopy use an opioid, a benzodiazepine or a combination of both. This study compares midazolam (M) (a benzodiazepine), alfentanil (A) (an opioid) and a combination of both drugs (M+A). One hundred and three patients were randomized in double-blind manner into groups M(35), A(33) and M+A(35). The number of coughs, number of additional aliquots of lignocaine and duration of the procedures were recorded along with oxygen desaturation. The patient's level of discomfort was assessed by patient and bronchoscopist and expressed as a visual analogue score. There were significantly fewer coughs per minute in Group A compared with Group M (P = 0.0053), and significantly less lignocaine was required in Group A (P = 0.005) and in Groups M+A (P < 0.002) compared with Group M. There was no significant difference in the assessment of discomfort between the groups. There was a trend for Group M+A to desaturate more than the other two with a significant difference between desaturation in Group M+A and Group A (P = 0.033). Alfentanil is a more effective anti-tussive agent than midazolam for outpatient fibre optic bronchoscopy. The combination of alfentanil and midazolam does not provide any better anti-tussive effect and may have the risk of a greater degree of desaturation secondary to increased sedation.

Clinical presentation and investigation of patients proceeding to isotope lung scanning for suspected pulmonary embolism.

The presenting features of 250 consecutive patients who underwent a ventilation/perfusion lung scan for suspected pulmonary embolus (PE) were analysed. Ninety-six patients had lung scans highly suggestive of PE, with one or more unmatched segmental perfusion defects (scan positive), 86 had low probability scans (scan negative) and 68 an indeterminate scan. Scan positive patients were more likely to have a PaO2 of less than 10.7 kPa, an elevated P(A-a)O2 and an abnormal chest X-ray compared with scan negative patients but these measurements were of poor specificity. Furthermore, scan-positive patients had a higher incidence of lung disease. Localized chest wall tenderness was more common in scan-positive patients, occurring in 9% of patients, but there were no other significant differences in individual symptoms, signs or electrocardiographic findings between scan-positive and scan-negative patients. The diagnosis of PE should not be made on clinical grounds alone and all patients suspected of having a PE should at least undergo isotope lung scanning.

Effect of gamma aminobutyric acid on the carbon dioxide rebreathing response of normal subjects: a study using vigabatrin.

Animal studies suggest that gamma aminobutyric acid (GABA) may be an important neurotransmitter in the control of respiration. Vigabatrin, a new drug for the treatment of epilepsy, is thought to exert its effect by increasing GABA concentrations in the brain. To assess the effect of increased GABA concentrations in the brain on human respiration we measured the ventilatory response to carbon dioxide in seven normal subjects after they had taken vigabatrin or placebo for three days in a double blind crossover study. There was no change in either the slope or the intercept of the curve of the ventilatory response to carbon dioxide after vigabatrin by comparison with placebo. This study suggests that GABA does not have an important role in the control of respiration in normal individuals.

Clinical pharmacokinetic considerations in the control of oral anticoagulant therapy.

Aspects of the pharmacokinetics of warfarin that are clinically relevant are reviewed here. Since warfarin is normally completely absorbed, resistance to treatment due to impaired absorption is unusual, even in severe short bowel syndrome. Warfarin is highly albumin-bound; thus, hypoalbuminaemic states result in an increased free fraction of the drug and a decreased half-life but, as might be expected, there is no evidence of altered response at steady-state. Warfarin is completely metabolised by the liver to hydroxy-warfarins and warfarin alcohols, and although the latter have some biological activity they do not contribute significantly to the drug effect. No information is available concerning the metabolism of warfarin in chronic liver disease, but there is evidence of increased sensitivity due to impaired vitamin K-dependent clotting factor synthesis. Impaired renal function does not appear to alter the effect of warfarin. Lowered response to the drug may be secondary to poor compliance, kinetic resistance or pharmacodynamic resistance. These factors can be identified using algorithms based on population values for plasma warfarin concentrations and clearances at steady-state. The pharmacokinetics and pharmacodynamics of warfarin indicate that several days' overlap with heparin on initiation of warfarin, and gradual (rather than sudden) discontinuation of warfarin, might theoretically be necessary. However, those studies which have been performed have indicated that a long overlap and gradual discontinuation are not associated with greater safety or efficacy of the drug. Because of the long elimination half-life of warfarin and the short elimination half-life of vitamin K, many days' treatment with phytomenadione may be required after warfarin overdose. The elimination half-life and therefore the duration of therapy may be reduced by regular oral cholestyramine, although the means by which the latter enhances warfarin elimination is still unknown.

Seasonal variation in suppressor T cell subsets and non-specific suppressor cell function in hay fever sufferers.

The helper/suppressor T cell ratio, as defined by monoclonal antibodies, was significantly higher in hay fever sufferers compared with controls (P less than 0.05), but only during or shortly after the pollen season. This was due to a reduction in the suppressor subset, which returned to control values in the winter. There was no significant difference in the non-specific concanavalin A-induced suppressor cell function compared with controls. The mean summer value was significantly lower than the winter value (P less than 0.05), but we cannot be sure that this was not the result of changes in laboratory conditions. No relationship was found between T cell subsets or suppressor cell function and total or specific IgE levels, or between T cell subsets and suppressor cell function. Our findings suggest that in hay fever, reduction in suppressor cell numbers and function is a secondary phenomenon.

Immunological changes associated with a successful outcome of pollen immunotherapy.

Changes in immunological measurements thought to be important in the mechanism of immunotherapy for hay fever were related to objective measurements of treatment outcome. Antigen-specific IgE and IgG, and T suppressor cell status, using monoclonal antibodies and a specific functional assay, were measured before and after immunotherapy. Treatment outcome was assessed using nasal and conjunctival challenge tests. Seventeen subjects received immunotherapy for 6 months. Nine showed a decrease in nasal and/or conjunctival sensitivity, compared with 2 of 13 control subjects (P less than 0.05). Subjects responding to immunotherapy had a significantly higher post treatment IgE level and a higher pre- and post-treatment IgG level than non-responders and controls. Immunotherapy had no effect on suppressor cell status.

The transfer factor and its subdivisions in patients with pulmonary emboli.

The carbon monoxide transfer factor and its subdivisions, the pulmonary membrane diffusing capacity and the pulmonary capillary volume were measured in fourteen subjects following submassive pulmonary emboli, as demonstrated by a ventilation-perfusion scan, and in fourteen matched controls. Transfer factor and alveolar volume were significantly lower in patients with pulmonary emboli (p less than 0.02). Patients were given six weeks anticoagulant therapy and the measurements repeated three months later. There was a significant increase in the transfer factor and the alveolar volume (p less than 0.01) and the membrane diffusing capacity (p less than 0.05). It has previously been assumed that the reduction in the transfer factor following a pulmonary embolus is due to a reduction in the pulmonary capillary volume. Results of this study however, suggest that it is more likely to be due to a loss of alveolar volume, at least in subjects with submassive emboli.

The effect of cigarette withdrawal on asthmatics who smoke.

Fourteen asthmatics volunteered to stop smoking. Seven managed to stop for only 24 h and seven for 1 week. There was a significant increase in peak flow and specific airways conductance as early as the first 24 h of abstention, while after 7 days of abstention there was a further increase in peak flow and specific airways conductance and a reduction in bronchial responsiveness to histamine. Two subjects felt that their symptoms were worse while abstaining and one of these showed an increase in bronchial responsiveness. After abstention for 1 week, four of the seven subjects recorded an improvement in symptoms. Asthmatics who smoke should be encouraged to stop. Despite an improvement in symptoms and objective measurements, asthmatics may find it difficult to stop smoking and will need considerable help and encouragement if they are to succeed.

Challenge tests and specific IgE in hay fever sufferers.

The relationship between challenge tests, specific IgE and seasonal effects in hay fever sufferers was studied. There were significant relationships between nasal challenge, conjunctival challenge and skin-prick test threshold doses, although the skin and conjunctiva tended to be less sensitive than the nose. A seasonal effect was apparent on nasal challenge, but not conjunctival challenge or skin-prick testing, with lower threshold doses recorded after the pollen season than in midwinter. There was a significant relationship between specific IgE and nasal challenge, but not conjunctival or skin-prick test threshold doses.

Histamine-induced suppressor cell function and nasal sensitivity in hay fever sufferers.

Histamine-induced suppressor cell function was measured in a group of twenty-five hay fever suffers and sixteen non-atopic controls. No difference was found in the suppression index between sufferers and controls. There was, however, a significant relationship between the suppression index and nasal sensitivity to grass pollen, whether measured pre- or post-season, but no correlation between specific or total IgE levels and the suppression index. Histamine-induced suppressor cell function may influence pollen sensitivity in the most sensitive subjects, but not via an effect on IgE production.

A comparison of 3 and 6 weeks' anticoagulation in the treatment of venous thromboembolism.

One hundred hospital in-patients treated for pulmonary embolism (PE) and/or deep vein thrombosis (DVT) were randomly allocated to receive 3 or 6 weeks' anticoagulation with heparin and warfarin. At one year recurrence rates were 12% in the 6 week group and 10% in those treated for 3 weeks. No patient died as a result of recurrence. Our study suggests that 3 weeks' anticoagulation therapy, using intravenous heparin for the first 5 days and warfarin from the third day, is adequate for patients without persisting risk factors.

Guidelines to control heparin treatment.

With new guidelines for the control of heparin infusion rates the proportion of kaolin cephalin clotting time ratios was significantly improved compared with ratios achieved without their use. Further improvement might result from careful preparation and delivery of the infusion.

Role of airway receptors in the breathing pattern of patients with chronic obstructive lung disease.

To determine whether airway receptors are responsible for the rapid, shallow breathing pattern seen in hypercapnic chronic obstructive lung disease, 10 patients underwent upper airway anaesthesia with inhaled lignocaine in a placebo controlled study. There was a significant reduction in breathing frequency after lignocaine (p less than 0.001) that was due to an increase in expiratory time (p less than 0.001). The inspiratory time remained unchanged, but tidal volume increased significantly (p less than 0.02). It is concluded that, while airway receptors may have a role in determining the frequency of breathing in chronic obstructive lung disease, other factors are responsible for the reduced inspiratory time.