P. John Rees

Circulating concentrations of histamine, neutrophil chemotactic activity, and catecholamines during the refractory period in exercise-induced asthma

Circulating mediators and catecholamine concentrations have been measured in eight subjects with asthma who were subjected to two bouts of cycle ergometer exercise separated by 1 hour. The maximum falls in FEV1 were 21.9 +/- 2.3% (mean +/- SEM; n = 8) and 5.5 +/- 1.3% (mean +/- SEM; n = 8) after the first and second exercises, respectively. Serum neutrophil chemotactic activity (NCA) and plasma histamine and catecholamine levels in venous blood were measured with a microchemotaxis and two radioenzymatic techniques, respectively. There was a significant increase in NCA and plasma histamine concentrations after both exercise challenges, and there was no significant difference in the release of these mediators between the two exercise tests. Gel filtration chromatography demonstrated that the NCA detected after the first and second exercise tests had molecular sizes of approximately 600,000 daltons. There was no significant time-dependent increase in plasma norepinephrine and epinephrine concentrations after either exercise task, even though the patients were refractory to exercise-induced asthma after the second exercise. These results suggest that the refractory period in exercise-induced asthma is not caused by mediator depletion, as indicated by NCA and histamine measurements, or by protection of the airways through catecholamine release.

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 β-agonists provide rapid relief of bronchoconstriction, whereas long-acting β-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 β-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.

Airway responsiveness to methacholine after inhalation of nebulized hypertonic saline in bronchial asthma

To assess whether the changes in airway methacholine (Meth) responsiveness induced by an initial hypertonic challenge determine the response to a subsequent hypertonic provocation, 11 subjects with asthma had bronchial challenges with 3.6% hypertonic saline (HS) and Meth in a dose-dependent manner and in random order. Challenges consisted of (1) an HS challenge (HS1) followed 1 hour later by a second HS challenge (HS2), (2) a Meth challenge alone (Meth1), and (3) an HS challenge followed 1 hour later by a Meth challenge (Meth2). The dose of HS that produced a 35% fall in SGaw (PD35) in HS1 was 69 L (geometric mean), and the PD35 in HS2 was 107 L (p = 0.02). Refractory index (PD35 HS2/PD35 HS1) ranged from 0.7 to 5.0. After HS challenge, airway responsiveness to Meth increased, and the Meth PD35 fell from 0.26 mumol to 0.11 mumol (geometric mean, p = 0.004). There was an inverse linear correlation between the refractory index and increases in Meth sensitivity (PD35 Meth1/PD35 Meth2) (r = -0.66; p = 0.027). After an initial HS challenge, the ratio of PD35 HS to PD35 Meth increased in all subjects, indicating that all subjects had become less responsive to HS compared to Meth, irrespective of their refractory index. We suggest that an initial HS challenge induces protective mechanisms toward a subsequent HS challenge in all individuals. The degree of increase in Meth responsiveness elicited by the initial provocation is a major factor in determining the airway response to a subsequent HS challenge.

Hill walkers' lung.

A previously healthy female presented with a 7-week history of dyspnoea on exertion following inhalation of a fluorochemical-based water repellent spray, which was applied to footwear, in the living area that she shared with 8 members of her family while on a hill walking holiday. Clinical examination, serial lung function studies, bronchoalveolar lavage, transbronchial biopsies and high-resolution CT thorax confirmed a sub-acute interstitial pneumonitis, which did not resolve until 15 weeks following exposure. None of her family members were affected despite similar exposure. Interstitial pneumonitis due to inhalation of fluorochemical-based water repellent, though rarely described, usually presents in an acute severe form necessitating immediate therapy and resolves in 1–4 weeks. Pulmonary fibrosis can also occur. Sub-acute interstitial pneumonitis following inhalation of fluorochemical-based water repellent spray should always be considered as a cause of unexplained persistent respiratory symptoms in otherwise healthy individuals involved in outdoor pursuits.

The natural history of asthma.

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Clinicians' Guide to Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease is often considered a rather dated disease but its prevalence continues to increase and the range of treatments to expand. Over the next 20 years the burden in developing countries will increase as they reap the effects of recent years of increased cigarette smoking. Timothy Howes has reviewed the available information in a clear and approachable short book. The text covers areas such as epidemiology, pathophysiology, diagnosis and prevention, before moving on to practical areas of management. The management covers important newer areas such as pulmonary rehabilitation, non-invasive ventilation and surgery for COPD as well as pharmacological treatment. The text is well referenced through a useful list of further reading at the end of each chapter. The radiographs need better reproduction to be very useful. The major part of COPD management at present is in primary care. A great deal of effort goes in to trying to prevent exacerbations which lead to expensive admissions to hospital and carry a high mortality. The effectiveness of some therapies in this area is described clearly. Hospital at home and early discharge teams have developed in many areas and this is included in the useful chapter on the primary-secondary care interface. However, this chapter repeats some of the treatment material from other chapters and tends to set primary care apart. Other chapters seem aimed more at secondary care with over five pages on lung reduction surgery and two out of the three final case studies decidedly hospital based. In England and Wales the arrangements for oxygen prescribing have just changed from primary to secondary care and this will warrant further coverage in subsequent editions. While there is plenty of useful information here it would be good to see more emphasis on a multidisciplinary approach and the issues of primary care where the majority of chronic obstructive pulmonary disease management should be based.