Ramon Orriols

Inhaled Tobramycin in Non—Cystic Fibrosis Patients with Bronchiectasis and Chronic Bronchial Infection with Pseudomonas Aeruginosa

BACKGROUND: Non—cystic fibrosis (CF) patients with bronchiectasis usually develop chronic bronchial infection with Pseudomonas aeruginosa (PA) that is related to worsening lung function and increased morbidity and mortality. OBJECTIVE: To determine whether direct aerosol delivery of tobramycin to the lower airways may control infection and produce only low systemic toxicity. METHODS: A double-blind, placebo-controlled crossover trial involving 30 patients was conducted to determine the clinical effectiveness and safety of 6-month tobramycin inhalation therapy. Patients received 300 mg of aerosolized tobramycin or placebo twice daily in 2 cycles, each for 6 months, with a one-month washout period. The number of exacerbations, number of hospital admissions, number of hospital admission days, antibiotic use, pulmonary function, quality of life, tobramycin toxicity, density of PA in sputum, emergence of bacterial resistance, and emergence of other opportunistic bacteria were recorded. RESULTS: The number of admissions and days of admission (mean ± SD) during the tobramycin period (0.15 ± 0.37 and 2.05 ± 5.03) were lower than those during the placebo period (0.75 ± 1.16 and 12.65 ± 21.8) (p < 0.047). A decrease in PA density in sputum was associated with tobramycin administration in the analysis of the first 6-month cycle (p = 0.038). No significant differences were observed in the number of exacerbations, antibiotic use, pulmonary function, and quality of life. The emergence of bacterial resistance and other bacteria did not differ between the 2 periods of study. Inhaled tobramycin was associated with bronchospasm in 3 patients, but not with detectable ototoxicity or nephrotoxicity. CONCLUSIONS: Aerosol administration of high-dose tobramycin in non-CF bronchiectatic patients for endobronchial infection with PA appears to be safe and decreases the risk of hospitalization and PA density in sputum. Nevertheless, pulmonary function and quality of life are not improved, and the risk of bronchospasm is appreciable.

Inhaled antibiotic therapy in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa

The aim of this study was to investigate the long-term effectiveness and safety of inhaled antibiotic treatment in non-cystic fibrosis patients with bronchiectasis and chronic infection by Pseudomonas aeruginosa, after standard endovenous and oral therapy for long-term control of the infection had failed. After completing a 2-week endovenous antibiotic treatment to stabilize respiratory status, 17 patients were randomly allocated to a 12-month treatment either with inhaled ceftazidime and tobramycin (group A) or a symptomatic treatment (group B). One patient from group A abandoned inhaled treatment because of bronchospasm and another from group B died before the end of the study. The remaining 15 patients, seven from group A and eight from group B, completed the study. Both groups had similar previous characteristics. The number of admissions and days of admission (mean +/- SEM) of group A [0.6 (1.5) and 13.1 (34.8)] were lower than those of group B [2.5 (2.1) and 57.9 (41.8)] (P < 0.05). Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), PAO2 and PACO2 were similar in the two groups at the end of follow-up, showing a comparable decline in these parameters. There were no significant differences either in the use of oral antibiotics or in the frequency of emergence of antibiotic-resistant bacteria between groups. Microbiological studies suggested that several patients had different Pseudomonas aeruginosa strains. None of the patients presented impaired renal or auditory function at the end of the study. This study suggests that long-term inhaled antibiotic therapy may be safe and lessen disease severity in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa which do not respond satisfactorily to antibiotics administered via other routes.

Reported occupational respiratory diseases in Catalonia

Objectives: A voluntary surveillance system was implemented in Catalonia (Spain) to ascertain the feasibility, incidence, and characteristics of occupational respiratory diseases and compare them with those of the compulsory official system. Methods: In 2002, in collaboration with the Occupational and Thoracic Societies of Catalonia, occupational and chest physicians and other specialists were invited to report, on a bimonthly basis, newly diagnosed cases of occupational respiratory diseases. Information requested on each case included diagnosis, age, sex, place of residence, occupation, suspected agent, and physician’s opinion on the likelihood that the condition was work related. Compulsory official system data derived from statistics on work related diseases for possible disability benefits declared by insurance companies, which are responsible for declaring these diseases to the Autonomous Government of Catalonia. Results: Of 142 physicians seeing patients with occupational respiratory diseases approached, 102 (74%) participated. Three hundred and fifty nine cases were reported, of which asthma (48.5%), asbestos related diseases (14.5%), and acute inhalations (12.8%) were the most common. Physicians rated 63% of suspected cases as highly likely, 28% as likely, and 8% as low likelihood. The most frequent suspected agents reported for asthma were isocyanates (15.5%), persulphates (12.1%), and cleaning products (8.6%). Mesothelioma (5.9%) was the most frequent diagnosis among asbestos related diseases. The number of acute inhalations reported was high, with metal industries (26%), cleaning services (22%), and chemical industries (13%) being the most frequently involved. The frequency of occupational respiratory diseases recorded by this voluntary surveillance system was four times higher than that reported by the compulsory official system. Conclusions: The compulsory scheme for reporting occupational lung diseases is seriously underreporting in Catalonia. A surveillance programme based on voluntary reporting by physicians may provide better understanding of the incidence and characteristics of these diseases. Persulphates and cleaning products, besides isocyanates, were the most reported causes of occupational asthma. Metal industries and cleaning services were the occupations most frequently involved in acute inhalations with a remarkably high incidence in our register.

Cocaine-induced churg-strauss vasculitis

A freebase cocaine-smoking woman developed relapsing fever, bronchoconstriction, arthralgias and weight loss. Pulmonary infiltrates, arthritis, microhaematuria, pruriginous skin rash and mononeuritis multiplex were later added to the clinical picture. Both skin and muscle biopsies showed eosinophilic angiitis. Improvement or worsening of her clinical picture repeatedly coincided with avoidance or use of smoked cocaine, respectively. We suggest that Churg-Strauss vasculitis may be a complication of smoking freebase cocaine.

A workforce-based study of occupational exposures and asthma symptoms in cleaning workers

Objectives To study associations between use of cleaning products and asthma symptoms in cleaning workers. Methods Information on respiratory symptoms, history of asthma, workplaces, use of cleaning products and acute inhalation incidents were obtained through a self-administered questionnaire. 917 employees of 37 cleaning companies in Barcelona were studied. 761 (83%) were current cleaners, 86 (9%) former cleaners and 70 (8%) had never worked as cleaners. Multivariable logistic regression analyses were used to evaluate the associations between specific exposures among current cleaners and wheeze without having a cold, chronic cough and current asthma. Associations with an asthma symptom score were also studied using negative binomial regression analyses to report mean ratios. Results After adjusting for sex, age, nationality and smoking status, the prevalence of current asthma was non-significantly higher among current (OR 1.9; 95% CI 0.5 to 7.8) and former cleaners (OR 1.9; CI 0.6 to 5.5) than in never cleaners. Cleaners working in hospitals during the last year had a significantly increased prevalence of wheeze, current asthma and a 1.8 (95% CI 1.2 to 2.8) times higher mean asthma score. Use of hydrochloric acid was strongly associated with asthma score (mean ratio 1.7; 95% CI 1.1 to 2.6). Use of ammonia, degreasers, multiple purpose products and waxes was also associated with asthma score. Conclusions Cleaning work in places with high demand for disinfection, high cleaning standards and use of cleaning products containing respiratory irritants is associated with higher risk of asthma symptoms. This suggests irritants have an important role in cleaning-related asthma.

Validation of specific inhalation challenge for the diagnosis of occupational asthma due to persulphate salts

Background: The significant value of tests used to certify the diagnosis of occupational asthma due to persulphate salts remains uncertain. Aims: To validate the specific inhalation challenge (SIC) test for the diagnosis of occupational asthma. Methods: Eight patients with occupational asthma due to persulphate salts, eight patients with bronchial asthma who were never exposed to persulphate salts, and ten healthy subjects were studied. Clinical history taking, spirometry, bronchial challenge with methacholine, skin prick testing to common inhalant allergens and persulphate salts, total IgE levels, and SIC to potassium persulphate were carried out in all subjects. The SIC used increasing concentrations of potassium persulphate (5, 10, 15, and 30 g) mixed with 150 g of lactose. Patients tipped the mixture from one tray to another at a distance of 30 cm from the face for 10 minutes in a challenge booth. Results: The SIC was positive in all subjects with persulphate induced asthma and in one patient with bronchial asthma who had never been exposed to persulphate salts. Sensitivity was 100% (95% CI 67.6 to 100) and specificity was 87.5% (95% CI 52.9–97.8) when patients with occupational asthma due to persulphate salts were compared with those with bronchial asthma never exposed to persulphate salts. Conclusions: SIC to persulphate salts performed according to the protocol described appears to be useful for the diagnosis of occupational asthma secondary to inhalation of this substance.

Montelukast and Churg-Strauss syndrome

Several cases of eosinophilic conditions including Churg-Strauss syndrome (CSS) have recently been reported in asthmatic patients being treated with antileukotriene receptor antagonists. One patient with CSS who experienced a clinical relapse after treatment with montelukast and two asthmatic patients who developed CSS while receiving montelukast treatment are described. In one case reduction in the dose of oral steroid preceded the onset of CSS. To our knowledge, no case of CSS relapse has previously been reported in association with leukotriene antagonists.

Time of exposure as a prognostic factor in avian hypersensitivity pneumonitis

Spirometric values were subsequently evaluated in 22 patients suffering from hypersensitivity pneumonitis caused by avian problems. First spirometric values were abnormal in 18/22 (82%) of patients. A restrictive pattern was observed in 16/22 (72%) of patients and an obstructive pattern in 6/22 (27%). The TLCO was reduced in all cases (12/12). Improvement or normalization of the respiratory function occurred 3.4 +/- 2.4 months after the avian contact had ceased. At the end of the follow-up, parameters were normal in 13/22 (59%) of patients. The restrictive pattern remained unchanged in 7/22 (32%), and the obstructive pattern persisted in 4/22 (18%) of the patients. The TLCO was normal in 6/12 (50%) of patients. Neither age nor treatment with corticosteroids (13 patients) had a significant influence upon the evolution of the lung function. However, total recovery or significant improvement was observed in 12/12 (100%) of patients who had been in contact with birds less than 2 years, in contrast to 6/10 (60%) of patients with more than 2 years of contact (P = 0.002).

Functional and biological characteristics of asthma in cleaning workers

OBJECTIVESnCleaning workers have an increased risk of asthma but the underlying mechanisms are largely unknown. We studied functional and biological characteristics in asthmatic cleaners and compared these to healthy cleaners.nnnMETHODSnForty-two cleaners with a history of asthma and/or recent respiratory symptoms and 53 symptom-free controls were identified. Fractional exhaled nitric oxide (FeNO) was measured and forced spirometry with reversibility testing was performed. Total IgE, pulmonary surfactant protein D and the 16xa0kDa Clara Cell secretory protein were measured in blood serum. Interleukins and other cytokines, growth factors, cys-leukotrienes and 8-isoprostane were measured in exhaled breath condensate. Information on occupational and domestic use of cleaning products was obtained in an interview. Associations between asthma status, specific characteristics and the use of cleaning products were evaluated using multivariable linear and logistic regression analyses.nnnRESULTSnAsthma was associated with an 8% (95% confidence interval (CI) 1-15%) lower postbronchodilator FEV1, a higher prevalence of atopy (42% vs. 10%) and a 2.9 (CI 1.5-5.6) times higher level of total IgE. Asthma status was not associated with the other respiratory biomarkers. Most irritant products and sprays were more often used by asthmatic cleaners. The use of multiuse products, glass cleaners and polishes at work was associated with higher FeNO, particularly in controls.nnnCONCLUSIONSnAsthma in cleaning workers is characterised by non-reversible lung function decrement and increased total IgE. Oxidative stress, altered lung permeability and eosinophilic inflammation are unlikely to play an important underlying role, although the latter may be affected by certain irritant cleaning exposures.

Skin tests in bird breeder's disease.

The diagnostic value of skin tests was assessed in 35 patients affected by bird breeders disease by comparing the results with those obtained in a group of 27 symptomless breeders and 10 symptomless unexposed individuals. Sterilised and diluted serum and lyophilised extracts of faeces prepared from the breeders own birds were injected intradermally. Skinprick tests using the same materials were carried out simultaneously. The intradermal test using serum showed a positive reaction in 18 out of 20 patients tested and in three out of 20 symptomless breeders (p less than 0.0005); later reactions occurred in eight of the patients and one of the symptomless breeders (p less than 0.01). A delayed reaction was seen in five of the patients and one of the symptomless breeders (p = 0.09). No positive reactions were recorded in symptomless unexposed individuals. Intradermal skin testing using extracts of faeces yielded an immediate reaction in 19 of 21 patients and in three of 11 symptomless breeders tested (p less than 0.001); a late reaction was seen in 18 of the patients and in five of the symptomless breeders (p less than 0.05). Delayed reactions occurred in 11 of the 21 patients tested, whereas no positive responses were seen in symptomless breeders (p less than 0.025). Skinprick tests gave negative results in all cases. Skin testing constitutes a simple, quick, and safe procedure that can assist the differential diagnosis between individuals with bird breeders disease and symptomless breeders, the immediate reaction being similar in its sensitivity to testing for serum precipitins but possessing greater specificity.