Asthma and asthma-like disorders

AbstractBronchial asthma is defined as a chronic inflammatory disease resulting in a reversible and variable bronchial obstruction. For the clinical diagnosis of the disease there are some key indicators but as there is no ‘gold standard’ a correct diagnosis will sometimes not be obtained. Examples are patients in a symptom-free stage, current medication interfering with the methods used, patients with asthma-like symptoms reporting lack of effect of bronchodilators and patients who are unable to perform a forced expiration in an airway function test. The prevalence of asthma is reported to be 5–10%. The prevalence of asthma-like symptoms may be double this.The term ‘asthma-like’ has been used to an increasing extent during the last few years, which may indicate an increasing awareness of the fact that asthma-like symptoms are not always classical asthma. In this overview some disorders with asthma-like symptoms, especially in adults, are presented. The spectrum of differential diagnoses in a clinic may depend on which doctor/specialist the patient is consulting. In an asthma and allergy clinic it has been found that the most common differential diagnoses are chronic obstructive pulmonary disease (COPD), non-asthmatic cough and sensory hyper-reactivity (SHR), a disorder which is sometimes mixed up with asthma due to similar symptoms (heavy breathing, cough, increased secretion, difficulty in getting air etc.) and similar trigger factors (smoke, strong scents, exercise, cold air etc.). Recently it has been suggested that a capsaicin inhalation test may be an objective test for identifying patients with SHR. In asthma effective treatment is available today but in asthma-like disorders, such as SHR, no effective therapy is available, underlining the need of further research for understanding the pathophysiological mechanisms

Exercise-induced respiratory symptoms are not always asthma

AbstractEighty-eight patients with a history of exercise-induced respiratory symptoms performed a maximal exercise test in order to study the reasons for stopping the test. There was a wide range of percentage maximal fall in peak expiratory flow (PEF), from minus 3% to 63%, mean 11%, recorded 0–30 min, mean 12 min after the break. In the controls the maximal decrease was 0–16%, mean 6%. Diagnostic criteria for asthma were fulfilled by 48 patients (55%). Of these patients 42% had a fall in PEF ≥ 15% (exercise-induced asthma). Of the non-asthma patients 10% had a fall ≥ 15%. The most common reason for stopping the exercise in the asthma group was breathing troubles (46%), the most common reason in the non-asthma group was chest pain/discomfort (35%). In about 20% of the patients dizziness and/or pricking sensations in arms or legs indicated hyperventilation as an additional reason for stopping the exercise. It is concluded that other kinds of reaction, than bronchial obstruction such as breathing troubles not directly related to bronchial obstruction and chest pain, may be important factors that can restrict physical capacity in patients with exercise-induced respiratory symptoms

Anaplastic thyroid carcinoma: three protocols combining doxorubicin, hyperfractionated radiotherapy and surgery

Patients with anaplastic thyroid carcinoma can rarely be cured, but every effort should be made to prevent death due to suffocation. Between 1984 and 1999, 55 consecutive patients with anaplastic thyroid carcinoma were prospectively treated according to a combined regimen consisting of hyperfractionated radiotherapy, doxorubicin, and when feasible surgery. Radiotherapy was carried out for 5 days a week. The daily fraction until 1988 was 1.0 Gy×2 (A) and 1989–92 1.3 Gy×2 (B) . Thereafter 1.6 Gy×2 (C) was administered. Radiotherapy was administered to a total target dose of 46 Gy; of which 30 Gy was administered preoperatively in the first two protocols (A and B), while the whole dose was given preoperatively in the third protocol (C). The therapy was otherwise identical. Twenty mg doxorubicin was administered intravenously weekly. Surgery was possible in 40 patients. No patient failed to complete the protocol due to toxicity. In only 13 cases (24%) was death attributed to local failure. Five patients (9%) ‘had a survival’ exceeding 2 years. No signs of local recurrence were seen in 33 patients (60%); 5 out of 16 patients in Protocol A, 11 out of 17 patients in Protocol B, 17 out of 22 patients in Protocol C (P=0.017). In the 40 patients undergoing additional surgery, no signs of local recurrence were seen in 5 out of 9 patients, 11 out of 14 patients and 17 out of 17 patients, respectively (P=0.005)

Mild experimental exacerbation of asthma induced by individualised low-dose repeated allergen exposure. A double-blind evaluation

AbstractLow doses of environmental allergens have been proposed to increase bronchial hyperreactivity in sensitised individuals, without causing immediate asthmatic reactions. The primary aim of the present study was to evaluate whether repeated low doses of allergen, that do not cause overt bronchoconstriction, cause augmented non-specific bronchial reactivity. A secondary aim was to evaluate whether any changes in reactivity are associated with increased variability of lung function, and whether signs of inflammatory activity could be found. To do this, mild asthmatic patients without regular symptoms, but with both immediate and late reactions in response to a high dose of inhaled cat allergen extract, were included in a double blind, placebo controlled, cross-over study in which a low dose of allergen was administered on four consecutive days (Monday to Thursday). The dose of allergen was individualised for each patient, and was calculated to be 25% of the total dose given to produce an immediate and late response at screening. Repeated low dose allergen exposure produced a significant increase in methacholine reactivity compared to placebo, whereas FEV1 in the morning did not significantly change during the allergen week. Each low dose allergen exposure caused small changes in FEV1 (approximately 7% drop), which was significant vs. placebo only on day 2 (Tuesday). During the allergen week, six of eight patients reported asthma symptoms on at least one occasion, and variability in lung function, measured with a portable spirometer, was increased. Repeated low doses of allergen also produced a significant increase of P-ECP vs. placebo, without a significant rise in circulating eosinophils. However, no significant changes in circulating CD3, CD4, CD8, CD19, or CD25 cells were found, evaluated by FACS analysis. We conclude that low doses of allergen produce signs of a mild exacerbation of asthma, including increased bronchial reactivity to methacholine. This clinical model may be useful to evaluate both the pathophysiological mechanisms of asthma, and the effects of novel anti-asthma drugs

Effect of topical corticosteroids on seasonal increases in epithelial eosinophils and mast cells in allergic rhinitis: a comparison of nasal brush and biopsy methods

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldBACKGROUND: Nasal brushing and nasal biopsy are well-tolerated sampling techniques. Seasonal grass pollen-induced rhinitis is characterized by epithelial mast cell infiltration and seasonal increases in both epithelial and sub-mucosal eosinophils. OBJECTIVE: To compare the ability of the nasal brush and nasal biopsy techniques to detect natural seasonal increases in eosinophils and mast cells, and to assess the influence of topical corticosteroid. METHODS: Nasal brush samples and nasal biopsies were collected from 46 grass pollen-sensitive seasonal rhinitis patients before the grass pollen season and at the peak of the pollen season following 6 weeks' treatment with either fluticasone propionate aqueous nasal spray (200 microg, twice daily) or placebo nasal spray. RESULTS: Placebo patients showed seasonal increases in epithelial eosinophils both with nasal brushing (P < 0.0001) and biopsy (P < 0.001). Epithelial mast cell numbers also increased during the pollen season as detectable by brushing (P < 0.0001) and biopsy (P < 0.03). Changes in cell numbers measured by nasal brushing correlated with those observed with nasal biopsy, both for eosinophils and mast cells (P < 0.05). Sub-mucosal eosinophils but not mast cells also increased during the pollen season (P < 0.002). Nasal brushing and biopsy revealed that fluticasone treatment inhibited seasonal increases in epithelial eosinophils (P < 0.00001) and epithelial infiltration by mast cells (nasal brushing P < 0.00001 and nasal biopsy P < 0.01). Fluticasone also inhibited seasonal increases in sub-mucosal eosinophils (P < 0.001) and significantly reduced nasal symptoms (P < 0.001). CONCLUSION: Nasal brushing harvests sufficient inflammatory cells from the surface of the nasal mucosa to be used in lieu of nasal biopsies in observation of the effect of drugs on the nasal epithelium

Airway sensory hyperreactivity linked to capsaicin sensitivity. Definitions and epidemiology.

Aims: • To study the relationship between odour intolerance and capsaicin sensitivity and to develop a definition of airway sensory hyperreactivity (SHR). • To study epidemiology of odour intolerance; particularly regarding airway symptoms, and to relate odour intolerance to possible risk factors. • To investigate the relationships between SHR and other respiratory diseases. • To study psychiatric morbidity at SHR. Material and methods: Totally 2847 adult subjects were included in these studies; 55% of them were women and 897 were patients. Studies I and IV were performed among patients referred to the Allergy Centre at the Central Hospital of Skövde, Sweden. Study IV also included a group of asthma patients from three Care Centres. Study II was a cross-sectional, population-based epidemiological study of adult inhabitants in Skövde, and in study III randomly selected individuals from this population-based study were used. In all four studies, we used questionnaires to evaluate the symptoms arising from odour exposure, the consequences of these symptoms for the participants’ social lives, and smoking habits. Olfactory function was evaluated in study II. Patients referred to the Allergy Centre were diagnosed with medical history, allergy investigations, and nose and pulmonary function tests when appropriate. In study IV methacholine tests were performed in patients with SHR in order to exclude asthma. Capsaicin inhalation tests were used in study I, III and IV. Results: The limiting value for the capsaicin inhalation test was defined as 35 coughs after provocation with a concentration of either 0.4 or 2.0 µM capsaicin. The prevalence of SHR, defined as odour intolerance with affective and behavioural consequences and a positive capsaicin test, was estimated at 6% (95% CI: 4.2-8.4) in a general Swedish population. Odour intolerance with affective and behavioural consequences was reported by 19% (95% CI: 15-22), while one-third reported general odour intolerance. There was no evidence for an increased prevalence of SHR among asthma patients, an increased prevalence of asthma among SHR patients, any relationship between SHR and smoking, any relationship between SHR and depression or anxiety, nor any association between odour intolerance and changed sense of smell. Conclusions: The diagnosis “Airway sensory hyperreactivity” (SHR) is proposed for patients with airway symptoms and affective reactions to and behavioural consequences of odour intolerance, who also have a positive capsaicin inhalation test. Keywords: Capsaicin; chemical sensitivity; epidemiology; odour intolerance; sensory hyperreactivity; IBSN 978-91-628-7548-

Recruitment of CD1a+ Langerhans cells to the nasal mucosa in seasonal allergic rhinitis and effects of topical corticosteroid therapy

BACKGROUND: Local antigen presentation may be necessary for both primary and recall T-cell responses to grass pollen in hay fever patients. We examined the effect of seasonal allergen exposure on nasal mucosal antigen-presenting cell (APC) populations and the effects of topical corticosteroid therapy. METHODS: Nasal biopsies were collected from 46 grass pollen-sensitive seasonal rhinitis patients before the grass-pollen season. A second biopsy was collected during the pollen season, when patients had received 6 weeks' treatment with either fluticasone propionate (200 microg, twice daily) or placebo. Cell populations in biopsy sections were quantified by immunocytochemistry. RESULTS: Significant increases in submucosal and epithelial CD1a+ Langerhans cells, but not CD68 + macrophages or CD20 + B cells, were observed during the pollen season. Seasonal increases in CD1a+ Langerhans cells were inhibited by corticosteroid therapy. CONCLUSIONS: Recruitment of CD1a+ Langerhans cells to the nasal mucosa during natural seasonal allergen exposure may contribute to local T cell responses. Topical corticosteroids may act, at least in part, by inhibiting effective allergen presentation to T cells through inhibition of recruitment of Langerhans cells to the nasal mucos