Systemic sensitivity to corticosteroids in smokers with asthma.

Cigarette smokers with asthma are insensitive to the therapeutic effects of corticosteroids. It is not known whether this insensitivity to corticosteroids in smokers affects tissue sites beyond the airways. A total of 75 asthmatic subjects (39 smokers) and 78 healthy controls (30 smokers) were recruited to an observational study. The cutaneous and peripheral blood lymphocyte responses to corticosteroids were measured. The cutaneous vasoconstrictor response to topical beclometasone was measured by applying different concentrations of beclometasone solutions to the skin in a random double-blind manner. The degree of blanching at each concentration was graded after 18 h. The sensitivity of peripheral blood lymphocytes to corticosteroids was assessed by measuring the suppressive effect of dexamethasone on lymphocyte proliferation stimulated by phytohaemagglutinin (PHA). Total mean+/-sd cutaneous vasoconstrictor response score to beclometasone was reduced in smokers with asthma to 5.39+/-3.58 versus 7.26+/-3.05 in never-smokers with asthma; and in all smokers to 6.47+/-3.33 versus 7.86+/-2.81 in all never-smokers. The sensitivity to corticosteroids of lymphocytes stimulated by PHA was similar between groups. In conclusion, smokers with asthma have an impaired cutaneous vasoconstrictor response to topical corticosteroids compared with never-smokers with asthma. This finding suggests that the insensitivity to corticosteroids in smokers with asthma affects tissue sites other than the airways.

Serum and sputum neurotrophin levels in chronic persistent cough.

BACKGROUND: Neurotrophins (NTs) are a family of growth factors, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin3 (NT-3) that are involved in inflammation. Serum and induced sputum NT levels are increased in asthma and in cough because of idiopathic pulmonary fibrosis, respectively. Neurogenic inflammation is implicated in the pathogenesis of chronic cough in individuals with normal chest radiography, but the role of NTs in this condition is unknown. OBJECTIVE: To assess if NT levels are elevated in the serum and airways in subjects with chronic persistent cough. METHODS: Eighty-one subjects with chronic cough persistent for over 1 year; with normal chest radiography and spirometry were included. Thirty healthy subjects were controls. Serum NGF, BDNF and NT-3 were measured by enzyme immunoassay. In a subset, NGF was measured in induced sputum. Sputum cell counts and allergen-specific serum IgE were measured and all patients received specific sequential treatment trials to achieve a final diagnosis for the cough. RESULTS: There was no significant difference either in the levels of serum or sputum NTs in chronic cough subjects compared with controls or between the most common causes of cough: post-nasal drip syndrome, gastro-oesophageal reflux disease, asthma and bronchiectasis. The median (inter-quartile range) for sputum NGF (pg/mL) was 516 (296-772) in healthy controls and 580 (312-880) in subjects with chronic cough (P=0.284). There was no correlation between NT levels and sputum cell counts. Sputum NGF levels correlated with duration of cough (r=0.34, P=0.002). CONCLUSION: NTs are not elevated in induced sputum or serum of subjects with chronic persistent cough. This implies that NTs do not have a central role in perpetuating airway inflammation in chronic persistent cough.

Influence of cigarette smoking on inhaled corticosteroid treatment in mild asthma.

BACKGROUND: Although inhaled corticosteroids have an established role in the treatment of asthma, studies have tended to concentrate on non-smokers and little is known about the possible effect of cigarette smoking on the efficacy of treatment with inhaled steroids in asthma. A study was undertaken to investigate the effect of active cigarette smoking on responses to treatment with inhaled corticosteroids in patients with mild asthma. METHODS: The effect of treatment with inhaled fluticasone propionate (1000 microg daily) or placebo for 3 weeks was studied in a double blind, prospective, randomised, placebo controlled study of 38 steroid naïve adult asthmatic patients (21 non-smokers). Efficacy was assessed using morning and evening peak expiratory flow (PEF) readings, spirometric parameters, bronchial hyperreactivity, and sputum eosinophil counts. Comparison was made between responses to treatment in non-smoking and smoking asthmatic patients. RESULTS: There was a significantly greater increase in mean morning PEF in non-smokers than in smokers following inhaled fluticasone (27 l/min v -5 l/min). Non-smokers had a statistically significant increase in mean morning PEF (27 l/min), mean forced expiratory volume in 1 second (0.17 l), and geometric mean PC20 (2.6 doubling doses), and a significant decrease in the proportion of sputum eosinophils (-1.75%) after fluticasone compared with placebo. No significant changes were observed in the smoking asthmatic patients for any of these parameters. CONCLUSIONS: Active cigarette smoking impairs the efficacy of short term inhaled corticosteroid treatment in mild asthma. This finding has important implications for the management of patients with mild asthma who smoke.

High resolution computed tomographic assessment of airway wall thickness in chronic asthma: reproducibility and relationship with lung function and severity.

BACKGROUND: In some patients chronic asthma results in irreversible airflow obstruction. High resolution computed tomography (HRCT) has been advocated for assessing the structural changes in the asthmatic lung and permits investigation of the relationships between airway wall thickening and clinical parameters in this condition. METHODS: High resolution CT scanning was performed in 49 optimally controlled asthmatic patients and measurements of total airway and lumen diameter were made by two independent radiologists using electronic callipers. Wall area as % total airway cross sectional area (WA%) and wall thickness to airway diameter ratio (T/D) were calculated for all airways clearly visualised with a transverse diameter of more than 1.5 mm, with a mean value derived for each patient. Intra- and inter-observer variability was assessed for scope of agreement in a subgroup of patients. Measurements were related to optimum forced expiratory volume in 1 second (FEV1), forced mid expiratory flow, carbon monoxide gas transfer, two scores of asthma severity, airway inflammation as assessed with induced sputum, and exhaled nitric oxide. RESULTS: Neither observer produced a statistically significant difference between measurements performed on two occasions but there was a significant difference between observers (limits of agreement -2.6 to 6.8 for WA%, p<0.0001). However, mean WA% measured on two occasions differed by no more than 5.4% (limits of agreement -4.0 to 5.4; mean (SD) 0.7 (2.4)). Statistically significant positive associations were observed between both WA% and T/D ratio and asthma severity (r(S)=0.29 and 0.30, respectively, for ATS score), and an inverse association with gas transfer coefficient was observed (r(S)=-0.43 for WA% and r(S)=-0.41 for T/D). No association was identified with FEV1 or airway inflammation. CONCLUSIONS: The airway wall is thickened in more severe asthma and is associated with gas transfer coefficient. This thickening does not relate directly to irreversible airflow obstruction as measured with FEV1.

Laboratory animal allergy: anaphylaxis from a needle injury.

A 32 year old male research physician accidentally received a minor wound from a needle which had been previously used on rabbit tissue. Within 15 minutes serious anaphylactic reactions started and he was taken to hospital where his condition stabilised within five hours. Serum immunoglobulin E antibodies to rabbit epithelium were high (16.2 U/ml), although other antibody titres were low. Allergy tests were not carried out before employment, so this alarming scenario could not have been predicted. People with confirmed laboratory animal allergy should be warned of the dangers of continued unprotected exposure and avoidance of the allergen should be encouraged by good laboratory practice and respiratory protective equipment.

Pulmonary infiltration after exposure to home renovation dust: histopathology and microanalysis.

A subacute self-resolving illness associated with bilateral pulmonary infiltration developed in a patient following renovation in her home. This may have been related to exposure to silicaceous plaster dust which was found in an environmental sample as well as on microanalysis of a transbronchial lung biopsy specimen and bronchoalveolar lavage fluid.

Sump bay fever: inhalational fever associated with a biologically contaminated water aerosol.

OBJECTIVE: To investigate the clinical, serological, and environmental features of a work related inhalational fever associated with exposure to an aerosol generated from a biologically contaminated 130,000 gallon water pool in a building used for testing scientific equipment. METHOD: Cross sectional survey of all exposed subjects (n = 83) by symptom questionnaire, clinical examination, spirometry, and serology for antibody to Pseudomonads, pool water extract, and endotoxin. In symptomatic patients diffusion capacity was measured, and chest radiology was performed if this was abnormal. Serial peak flow was recorded in those subjects with wheeze. Bacterial and fungal air sampling was performed before and during operation of the water pool pump mechanism. Endotoxin was measured in the trapped waters and in the pumps. Serum cotinine was measured as an objective indicator of smoking. RESULTS: Of the 20 symptomatic subjects, fever was most common in those with the highest exposure (chi 2 42.7, P < 0.001) in the sump bay when the water was (torrentially) recirculated by the water pumps. Symptoms occurred late in the working day only on days when the water pumps were used, and were independent of the serum cotinine. Pulmonary function was normal in most subjects (spirometry was normal in 79/83, diffusion capacity was low in five subjects, chest radiology was normal). Peak flow recording did not suggest a work relation. The bacterial content of the aerosol rose from 6 to > 10,000 colony forming units per cubic metre (cfu/m3) (predominantly environmental Pseudomonads) when the pumps were operating. High endotoxin concentrations were measured in the waters and oil sumps in the pumps. Low concentrations of antibody to the organisms isolated were detected (apart from two subjects with high antibody) but there was no relation to exposure or the presence of symptoms and similar antibody was found in the serum samples from a non-exposed population. The fever symptoms settled completely with the simple expedient of changing the water and cleaning the pumps. CONCLUSION: Given the results of our study, the development of inhalational fever in this unique environment and clearly restricted cohort was closely related to the degree of exposure to contaminated aerosol and mainly occurred in the absence of distinct serological abnormality and independent of cigarette smoking.

A comparison of the seroepidemiology of chlamydial infection in pigeon fanciers and farmers in the U.K.

A detailed comparative seroepidemiological study of antibody responses was performed in 271 pigeon fanciers and 100 farmers. Overall 73% of pigeon fanciers had IgG antibodies at a titre greater than or equal to 16 to Chlamydia pneumoniae, 39% to Chlamydia psittaci, and 6.6% to Chlamydia trachomatis. The prevalence of chlamydial antibodies was significantly lower in the farmers at 47% for C. pneumoniae, 6% for C. psittaci, and 2% for C. trachomatis. Both populations were exposed to complex microbiological and antigenic environments: 50.5% of the pigeon fanciers had antibodies to pigeon antigens, 34% to egg membrane, and 0.73% to yolk sac antigen, and 59% of the farmers had antibodies to Micropolyspora faeni, but the high prevalence of chlamydial antibodies could not be attributed to interaction with these antigens. There was considerable overlap of chlamydial antibody responses in the pigeon fanciers but not in the farmers: 36% of the pigeon fanciers had antibodies to C. pneumoniae alone, 5% to C. psittaci alone, and 31% to both agents, whereas only 3% of farmers had antibodies to both C. pneumoniae and C. psittaci. The high prevalence of antibodies to C. psittaci in the pigeon fanciers is compatible with the known avian reservoir for this infection. The particularly high prevalence of antibodies to C. pneumoniae suggests that complex interactions may be occurring in a population exposed to two chlamydial organisms, whereby infection with one species may provoke an anamnestic response against other chlamydial organisms with which the subject has previously been infected.

Comparison of the inhibitory effect of propofol, thiopentone and midazolam on neutrophil polarization in vitro in the presence or absence of human serum albumin.

Anaesthetic agents inhibit some aspects of immune function and this may be clinically important when prolonged infusions are used in an intensive care unit. We have studied the effects of propofol, thiopentone and midazolam on neutrophil polarization in vitro. At concentrations seen in plasma during anaesthesia, propofol and thiopentone produced significant (approximately 50%) and comparable degrees of inhibition. Inhibition was complete with greater concentrations of these drugs. When compared with equivalent concentrations of midazolam, propofol produced more inhibition (P less than 0.01) at all concentrations investigated, except the smallest. Midazolam produced no effect at clinically relevant concentrations. The effect of propofol was not attributable to its lipid carrier vehicle, as 10% Intralipid alone augmented neutrophil polarization. Human serum albumin conferred some degree of protection against the inhibition produced by clinically relevant concentrations of propofol and thiopentone, but not that produced by greater concentrations of these drugs.

Climate, intermittent humidification, and humidifier fever.

Two summer outbreaks of humidifier fever (HF) are described in a microprocessor factory (factory A) and a printing factory (factory B). The air in each factory was humidified intermittently and controlled by present humidistats operating to maintain a relative humidity of 45% by an air handler incorporating a spray humidifier in factory A and two ceiling mounted spray humidifiers in factory B. Questionnaire data from each workforce suggested that although symptoms apparently occurred most commonly in both factories on return from holiday (41/57, 71.9%), many subjects (24/40, 60%) in factory A also had intermittent symptoms of ill defined periodicity for some time before the disorder was recognised. Similar intermittent symptoms with no discernible pattern occurred in factory B in a smaller number of subjects (4/17, 23.5%), all of whom were night or rotating shift workers. Both episodes of humidifier fever after return from summer holiday developed when nocturnal air temperatures were unseasonably low; not on the day of return to work but two days later (factory A) and one day later (factory B). Symptoms were most common in most workers who had circulating serum IgG antibody measured by ELISA to humidifier sludge in factory B (14/17, 82.9%) but were most common in IgG antibody negative subjects in factory A (27/40, 67.5%). A more classic form of humidifier fever redeveloped in factory B during winter when meteorological recordings suggested that humidification of intake air was more continuous. Humidifier fever in winter may have been the major influence on the formulation of the symptom pattern thought to be relevant for recognition of the disorder. A form of the illness, however, can occur during the summer which is camouflaged by intermittent humidification when the symptoms appear to be more closely associated with cool nocturnal air intake and unrelated to the pattern of attendance at work.