Use of dry powder inhalers in COPD.

INTRODUCTION: This was a study of 30 chronic obstructive pulmonary disease (COPD) patients to assess the ease of use and preference of four dry powder inhalers -- accuhaler, aerolizer, handihaler, turbohaler -- the accuhaler and turbohaler are multidose devices, whereas the aerolizer and handihaler are single dose devices. METHOD: None of the subjects had previous experience of dry powder inhalers. The correct technique for each inhaler was divided into 12 steps including one critical step that if not performed would result in no drug delivery. Subjects were shown the correct technique for each inhaler in a random order and were assessed immediately and 1 h later. Each subject was asked to rank the four devices for preference and ease of use, as well as to assess how comfortable it felt to inhale through the device using a visual analogue scale. RESULTS: The numbers of perfect scores were not significantly different between devices, but the number of fatal errors that would result in no drug delivery was significantly more common in single dose devices (p < 0.01). There were significant differences in the rankings of each device (Friedman test, p < 0.005) with the turbohaler being ranked first most often and the handihaler last. The turbohaler scored highest for comfort of inhalation and the accuhaler lowest, but differences were small. CONCLUSIONS: In COPD patients starting on dry powder inhalers, multidose devices appear to be preferred, have fewer problems and are easier to use effectively.

Snoring, not just a social nuisance.

Snoring is a very common source of complaints from partners and neighbours. Snorers themselves are less likely to be affected, unless they have associated daytime sleepiness caused by the sleep disruption from obstructive sleep apnoea. There is increasingly firm evidence that obstructive sleep apnoea is associated with hypertension, cardiovascular, cerebrovascular and metabolic problems such as insulin resistance, even at mild levels which may not cause much daytime somnolence. In addition, the central and obstructive apnoeas found in cardiac failure affect heart muscle function. Treatment of the apnoea improves blood pressure and cardiac function and is likely to have a beneficial effect on mortality. Since obstructive sleep apnoea is common it should be sought by appropriate questioning in these patient groups. The treatments for obstructive sleep apnoea are effective but cumbersome and this remains a challenge if patients do not achieve obvious early benefits such as reduction in sleepiness or breathlessness.

Computer assisted learning is an effective way of teaching endocrinology.

OBJECTIVES: Computers are a part of everyday life and offer an exciting way of learning. The aim of our study was to determine the effectiveness of teaching undergraduate endocrinology using a Computer Assisted Learning (CAL) programme. DESIGN AND SUBJECTS: One hundred and eighty-five first year clinical medical students were randomly assigned either to attend a series of conventional lectures (n = 77) or to have the same material available through a CAL programme. MEASUREMENTS: A multiple choice question examination was performed before and after the course. Lecture attendance and individual usage of the computer system were recorded. Students were asked to fill in an evaluation form at the end of the study. RESULTS: There was no significant difference in the first examination scores between the groups. Both groups improved their scores after the course. Students spent longer performing CAL than attending lectures. Those who scored lowest in the first examination spent the most time on the CAL course. Those who spent the most time on the CAL course showed the largest improvement in examination score. Thirty-six out of the 42 students, who completed an evaluation of the CAL programme, rated it better than the standard lectures. CONCLUSIONS: Computer assisted learning is an effective way of increasing knowledge in teaching undergraduate endocrinology. The course was easy to run and was valued more highly than conventional lectures. The module is now running routinely in the year 3 clinical firms at St Thomas' and has resulted in an increase in knowledge in the end of firm assessment.

Pulmonary echinococcosis with chest wall involvement in a patient with no apparent risk factors.

Pulmonary hydatid disease is rare in the U.K., and chest wall involvement has to our knowledge not previously been described in this country. We report the case of a 72-year-old man who was found to have a left upper lobe opacity on his chest radiograph. He declined further investigation at the time, but 2 years later developed a palpable mass over his left lateral chest wall. Fine-needle aspiration-biopsy of this mass revealed the diagnosis of pulmonary hydatid disease. Despite thorough questioning, no risk factor could be identified for the development of the disease. Hydatid disease should be remembered as a rare cause of mass lesions identified on chest radiographs even in non-endemic regions. Spread to the chest wall may mimic malignancy.

Inspiratory muscle strength in acute asthma.

STUDY OBJECTIVES: The aim of this study was to measure inspiratory pressure-generating capacity in patients presenting with acute asthma, as it has been suggested that inspiratory muscle fatigue may contribute to breathlessness and acute respiratory failure. DESIGN: Descriptive study. SETTING: Emergency departments of two inner-city hospitals. PATIENTS: Fifty-one patients with acute asthma, and 45 patients without respiratory disease who served as control subjects. MEASUREMENTS AND RESULTS: Maximum inspiratory pressure-generating capacity was measured soon after presentation by the sniff nasal inspiratory pressure (SNIP) method. The mean (SD) SNIP was 110 cm H(2)O (23 cm H(2)O) in men with asthma (mean for control subjects, 126 cm H(2)O [25 cm H(2)O]; p < 0.05) and 80 cm H(2)O [24 cm H(2)O] in women with asthma (mean for control subjects, 105 cm H(2)O (26 cm H(2)O); p < 0.01). In a second study of simultaneous SNIP and intrathoracic pressure measurements in a group of patients with acute asthma (n = 10) and control subjects (n = 11), the effect of airways obstruction on SNIP was assessed. The measurement of sniff esophageal pressure was more negative than SNIP by approximately 16% in asthmatic patients and by 4% in control subjects. Taking account of the likely effect of airways obstruction on SNIP, the reduction in inspiratory pressure-generating capacity that was observed in these patients with moderately severe acute asthma was minor and was consistent with the modest hyperinflation observed. CONCLUSIONS: This study did not find evidence of inspiratory muscle weakness or fatigue in patients with moderately severe acute asthma presenting to the emergency department.

Clinical safety of SonoVue, a new contrast agent for ultrasound imaging, in healthy volunteers and in patients with chronic obstructive pulmonary disease.

RATIONALE AND OBJECTIVES: To evaluate the safety profile of SonoVue, a new echo-contrast agent based on stabilized sulfur hexafluoride (SF6) microbubbles, in healthy volunteers and in patients with chronic obstructive pulmonary disease (COPD). METHODS: Safety and tolerability of SonoVue were evaluated in 66 healthy volunteers during two placebo-controlled phase I studies (a single intravenous ascending-dose study in 36 volunteers given SonoVue doses of 0.003 to 0.12 mL/kg and a multiple-dose study in 30 subjects given cumulative doses of 0.15 to 0.6 mL/kg) and in 12 patients with COPD of various degrees of clinical severity, who were given SonoVue at a dosage of 4 mL (corresponding to 0.057 mL/kg in a 70-kg patient). Adverse events were monitored up to 48 to 72 hours after administration. All volunteers underwent extensive safety assessments (monitoring of vital signs, electrocardiogram, blood oxygen saturation, laboratory assessments, and Mini-Mental test) up to 24 to 72 hours after administration. In addition, patients with COPD underwent specific lung function tests, such as forced expiratory volume, forced vital capacity, and forced midexpiratory flow. RESULTS: No serious adverse events occurred throughout the study. All nonserious adverse events were minor, mild, and rapidly self-resolving. No difference in the incidence of adverse events was observed among the various dosages of SonoVue and between SonoVue and placebo. There were no clinically significant changes in any of the safety assessments. No statistically significant differences between SonoVue and placebo were observed in mean forced expiratory volume, forced vital capacity, or forced midexpiratory flow levels. No substantial changes from baseline in blood oxygen saturation were observed for either study agent at any postinjection time point. CONCLUSIONS: SonoVue showed a good safety profile both in healthy subjects and in patients with COPD.

Subepithelial immunopathology of the large airways in smokers with and without chronic obstructive pulmonary disease.

Previous work has shown an increase in CD8+ T-cells, neutrophils and eosinophils in small airway subepithelium in smokers. The authors have now investigated whether similar changes occur in the large airways. Immunohistochemistry on frozen sections of bronchial biopsies were obtained at bronchoscopy in 11 nonsmokers, eight asymptomatic smokers and 11 smokers with chronic bronchitis and chronic obstructive pulmonary disease (COPD). There was an increase in the number of CD8+ cells infiltrating the bronchial subepithelium in the COPD group compared to the asymptomatic smokers (305 (109-400) versus 92 (41-550) cells x mm(-2), p=0.030). There was a negative correlation between the number of CD8+ cells and the forced expiratory volume in one second (FEV1) %predicted (p=0.005, r=-0.62), and a positive correlation between the number of CD8+ cells and the number of pack years smoked (p=0.017, r=0.42). There was a negative correlation between the activated/total eosinophils ratio and the FEV1 % pred (p=0.017, r=-0.51). There was a negative correlation between pack years smoked and the number of neutrophils (p=0.022, r=-0.36). Smokers who develop chronic obstructive pulmonary disease have increased numbers of CD8+ T-cells in large airways when compared to asymptomatic smokers. Airway obstruction was associated with an increase in the proportion of eosinophils that were activated.

Current treatment of asthma--focus on leukotrienes.

Since their identification in 1979, the cysteinyl leukotrienes (cysLTs) have been shown to be prominent in many inflammatory conditions, including asthma, allergic rhinitis, rheumatoid arthritis, psoriasis, cystic fibrosis and inflammatory bowel disease. They are potent pro-inflammatory agents, as well as causing bronchoconstriction, and undoubtedly have a role in asthma. The cysLTs are products of arachidonic acid metabolism and have been shown to have effects via a cysteinyl leukotriene receptor (CysLTR1) on vascular permeability, mucus production, chemotaxis and bronchial smooth muscle. Their detection in certain body fluids in allergic, aspirin-sensitive and exercise-induced asthma is well documented and potential roles in pathogenesis, proposed. The development of agents affecting production or action offers an exciting new approach to the treatment of asthma. Two approaches to antileukotriene therapy have been developed: blocking their production by inhibiting the action of 5-lipoxygenase enzyme or blocking the CysLTR1. Both approaches have been tried in studies in asthma and overall the results are encouraging, with a decrease in both daytime and nocturnal symptoms, a decrease in additional beta 2 agonist usage and improvement in lung function. The changes, however, are small in some studies. This may be a reflection of disease severity in the study subjects, but of note is a heterogeneity of response to these treatments that may be genetically determined. Antileukotriene therapy has been shown to have an effect in specific types of asthma where the role of cysLTs seems well established--aspirin-sensitive/intolerant asthma and exercise-induced asthma. Longer term studies are needed in other areas such as severe asthma and chronic persistent asthma in both children and adults to provide evidence for the appropriate placement of antileukotriene treatment in current asthma guidelines, in comparison with other established treatments.

Drug treatment of asthma in the 1990s: achievements and new strategies.

Asthma is an inflammatory condition of the airways. First-line therapy involves the use of inhaled corticosteroids as anti-inflammatory agents to control the underlying process. Bronchodilators are used for symptom relief. Short-acting beta-agonists provide rapid relief of bronchoconstriction, whereas long-acting beta-agonists control the symptoms and reduce the frequency of exacerbations when combined with inhaled corticosteroids. Anticholinergic bronchodilators have a minor role in acute exacerbations and in patients troubled by adverse effects from beta-agonists. Theophylline has a bronchodilator action in asthma, but its role as an anti-inflammatory agent needs to be examined further. Because of their toxicity, corticosteroid-sparing agents have a limited role, being restricted to patients with severe uncontrolled asthma. New selective phosphodiesterase IV inhibitors show both anti-inflammatory and bronchodilator characteristics with fewer adverse effects. Other new approaches to the control of inflammation come from the antileukotriene drugs, which improve pulmonary function in patients with chronic asthma. The antileukotrienes have shown promising results, especially in the treatment of asthma caused by aspirin (acetylsalicylic acid), exercise and cold air. Other new therapies being studied include anti-immunoglobulin E, antitryptase and anti-CD4 agents. These newer possibilities suggest that the range of available treatment options will expand significantly over the next decade.

A case of severe reversible lung disease caused by sulphasalazine.

Various lung problems have been reported in patients with inflammatory bowel disease. Some of these can be drug related. We report an unusual case of upper lobe infiltration which appeared to be caused by sulphasalazine.

An unusual cause of falls in an elderly patient.

Falls are common in the elderly, often causing considerable morbidity and mortality. Prevention is therefore important and is based on determining the cause. We present an elderly patient who had multiple falls during the day due to recurrent daytime sleep episodes, an entity we believe has not previously been reported.

Immunopathology of the small-airway submucosa in smokers with and without chronic obstructive pulmonary disease.

The airflow obstruction in chronic obstructive pulmonary disease (COPD) occurs mainly at the level of the small airways. In order to investigate the effect of smoking on small-airway submucosal immunopathology, we used immunohistochemistry in peripheral lung sections obtained at surgery from a group of smokers (n = 22) and from a group of nonsmokers (n = 22) that contained both ex-smokers (n = 17) and lifelong nonsmokers (n = 5). Subjects were also divided into those with (n = 19) and those without (n = 20) airflow obstruction. We found an increase in total eosinophils (p = 0.001) and activated eosinophils (p = 0.010), an increase in the CD8(+)/CD3(+) cell ratio (p = 0.003), and a decrease in the CD4(+)/CD8(+) cell ratio (p = 0.005) among cells infiltrating the small-airway submucosa in an area 50 micrometers deep to the basement membrane in smokers as compared with nonsmokers. There was also an increase in neutrophils (p = 0.019) when smokers were compared with lifelong nonsmokers. Neutrophil numbers correlated with numbers of eosinophils (p = 0.0003, r = 0.58). Furthermore, the CD8(+)/CD3(+) cell ratio was related to pack-years smoked (p = 0.016, r = 0.36), months since smoking cessation (p = 0.003, r = 0.47), and number of infiltrating eosinophils (p = 0.007, r = 0.43) and neutrophils (p = 0.004, r = 0.44). These findings suggest that smoking induces movement of an inflammatory infiltrate into the submucosa of the small airway, the location of the increased resistance to airflow in COPD.