Quality indicators in the rational management of severe asthma: A Spanish multidisciplinary consensus.

AIM: Severe asthma is a complex, heterogeneous condition that can be difficult to control despite currently available treatments. Multidisciplinary severe asthma units (SAU) improve control in these patients and are cost-effective in our setting; however, their implementation and development can represent an organizational challenge. The aim of this study was to validate a set of quality care indicators in severe asthma for SAU in Spain. METHODS: The Carabela initiative, sponsored by SEPAR, SEAIC, SECA and SEDISA and implemented by leading specialists, analyzed the care processes followed in 6 pilot centers in Spain to describe the ideal care pathway for severe asthma. This analysis, together with clinical guidelines and SEPAR and SEAIC accreditation criteria for asthma units, were used to draw up a set of 11 quality of care indicators, which were validated by a panel of 60 experts (pulmonologists, allergologists, and health-policy decision-makers) using a modified Delphi method. RESULTS: All 11 indicators achieved a high level of consensus after just one Delphi round. CONCLUSIONS: Experts in severe asthma agree on a series of minimum requirements for the future optimization, standardization, and excellence of current SAUs in Spain. This proposal is well grounded on evidence and professional experience, but the validity of these consensus indicators must be evaluated in clinical practice.

Mould and grass pollen allergy as risk factors for childhood asthma in Zaragoza, Spain

OBJECTIVE: Examine the prevalence of asthma and associated predictive factors in a group of 468 students. PATIENTS AND METHODS: A descriptive, cross-sectional observational study in a randomly selected population of 468 children aged 10-12, in the city of Zaragoza. We used the ISAAC questionnaire on asthma completed by children under supervision of the investigators. We assessed the genetic risk (family history of asthma) and environmental risks. The risk for atopy was assessed by the presence of positive skin prick tests. RESULTS: 25.3% of the children had symptoms consistent with asthma in the city of Zaragoza. Among them 33.1% reported a history of asthma in close relatives (OR=1.78, p < 0.001). The history of hospitalisations for lower respiratory tract illness was strongly associated with the presence of asthma (OR=6.72, p < 0.0001). Positive skin tests to Alternaria (OR=2.00, p < 0.0001) and grass pollen (OR=1.76, p < 0.001) were predictors of asthma. 63.6% of asthmatic children had presented clinical rhinitis in the previous 12 months, compared with 32% of non-asthmatics, and this difference was statistically significant (OR=3.89, p < 0.0001). 47% of asthmatics presented with or previously had eczema, whereas only 26.9% of non-asthmatics presented with or previously had these types of lesions (p < 0.0001). CONCLUSION: The following are predictors of asthma: History of hospital admissions for lower respiratory tract illness, presence of rhinitis and/or eczema, positive prick test for certain aeroallergens, especially Alternaria and grass pollen, and family history of asthma

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Mould and grass pollen allergy as risk factors for childhood asthma in Zaragoza, Spain.

OBJECTIVE: Examine the prevalence of asthma and associated predictive factors in a group of 468 students. PATIENTS AND METHODS: A descriptive, cross-sectional observational study in a randomly selected population of 468 children aged 10-12, in the city of Zaragoza. We used the ISAAC questionnaire on asthma completed by children under supervision of the investigators. We assessed the genetic risk (family history of asthma) and environmental risks. The risk for atopy was assessed by the presence of positive skin prick tests. RESULTS: 25.3% of the children had symptoms consistent with asthma in the city of Zaragoza. Among them 33.1% reported a history of asthma in close relatives (OR=1.78, p<0.001). The history of hospitalisations for lower respiratory tract illness was strongly associated with the presence of asthma (OR=6.72, p<0.0001). Positive skin tests to Alternaria (OR=2.00, p<0.0001) and grass pollen (OR=1.76, p<0.001) were predictors of asthma. 63.6% of asthmatic children had presented clinical rhinitis in the previous 12 months, compared with 32% of non-asthmatics, and this difference was statistically significant (OR=3.89, p<0.0001). 47% of asthmatics presented with or previously had eczema, whereas only 26.9% of non-asthmatics presented with or previously had these types of lesions (p<0.0001). CONCLUSION: The following are predictors of asthma: History of hospital admissions for lower respiratory tract illness, presence of rhinitis and/or eczema, positive prick test for certain aeroallergens, especially Alternaria and grass pollen, and family history of asthma.

Safety of triflusal (antiplatelet drug) in patients with aspirin-exacerbated respiratory diseases.

BACKGROUND AND AIMS: Aspirin, a cyclo-oxygenase (COX)-1 and COX-2 inhibitor, is the antiplatelet drug of choice to prevent serious vascular events. Adverse reactions to aspirin are frequent particularly among patients with asthma, chronic rhinosinusitis and nasal polyps. COX-1 inhibitors but not COX-2 inhibitors precipitate asthma attacks. Triflusal is a preferential COX-2 inhibitor antiplatelet agent that is as effective as aspirin in the prevention of serious vascular events. The aim of the study was to assess the tolerability of triflusal in patients with aspirin-exacerbated respiratory disease (AERD). METHODS: We studied 26 asthma patients [11 males, aged 52 (23-75) years] who had suffered asthma episodes triggered by one or more (23% of patients) nonsteroidal anti-inflammatory drugs. Aspirin sensitivity was confirmed by either intranasal or oral aspirin challenge. All subjects underwent a single-blind, placebo-controlled oral challenge with three doses of triflusal separated by 1 week (first cumulative dose = 225 mg; second cumulative dose = 450 mg; third cumulative dose = 900 mg). Cutaneous, respiratory, general symptoms and lung function were monitored for 4 h in the laboratory and for 24 h at home. RESULTS: No clinical reactions to triflusal were observed. There were no significant changes in lung function measurements. CONCLUSION: Our study appears to demonstrate that triflusal is a suitable alternative to aspirin as antiplatelet agent to prevent AERD.

[The specific bronchial provocation test in the diagnosis of occupational asthma]. / La prueba de provocación bronquial específica en el diagnóstico del asma ocupacional.

Specific bronchial challenge (SBC) testing is a key technique for diagnosing the origin of occupational asthma (OA). SBC is indicated in specific circumstances, including whenever several agents present in the work environment may be the cause of OA, when new or unusual occupational agents need to be identified, when evidence for legal action is required, or when research is conducted. SBC procedures are not standardized, because of the great diversity of occupational agents and the variety of physical and chemical properties involved. Thus, SBC testing with agents found in fumes, gases or vapors can be administered in special cabins or in closed circuits with continuous monitoring of sub-irritant concentrations. Agents found in dust, most but not all of which have high molecular weights, may be appropriate for routine SBC testing in an allergy laboratory. This paper will treat only these cases. SBC must be formed in specialized centers by experienced personnel, as it is a sophisticated and potentially dangerous technique. We describe a series of 20 patients diagnosed of OA in our unit over the past two years in whom SBC provided an etiologic diagnosis. All were exposed to dust or aerosols at work. The cause was a substance of high molecular weight in 17 cases, and low molecular weight in 3. The procedure used is described and models of bronchial response are discussed.

Hypersensitivity pneumonitis in workers exposed to esparto grass (Stipa tenacissima) fibers.

Esparto grass (Stipa tenacissima), which is commonly found in the Mediterranean countries, has a wide variety of uses. Five stucco makers who had cough, dyspnea, malaise, and fever after exposure to esparto fiber used in their jobs showed a significant decrease in symptoms when they were away from work. Precipitating antibodies against an esparto extract were found in the sera of all patients. Specific IgG antibodies against the esparto extract were also demonstrated in all patient sera, as were IgG antibodies to Aspergillus fumigatus and thermophilic microorganisms (Micropolyspora faeni and Thermoactinomyces vulgaris) by means of an ELISA method. Esparto activity was inhibited in different ranges by the above antigens by inhibition ELISA. Only A. fumigatus could be identified after microbiologic evaluation of the esparto fiber samples. After inhalation challenge tests were performed with esparto extracts, all patients showed significant decreases in forced vital capacity, transfer lung CO, and PaO2 blood gas from baseline values. Fever, chills, malaise, dry cough, tachycardia, tachypnea, and rales on chest auscultation were also observed in all patients. Findings from bronchoalveolar lavage were suggestive of allergic alveolitis. Transbronchial biopsy specimens showed interstitial alveolitis with lymphocyte-macrophage infiltrate and granuloma. Unexposed control subjects did not exhibit reactivity to any of the tests listed above. The dust derived from esparto fibers can cause hypersensitivity pneumonitis in exposed subjects. Organisms such as A. fumigatus and thermophilic actinomyces could be the causative antigens. "Stipatosis" might be an appropriate name for this disorder.

Occupational asthma induced by aniseed.

This report deals with clinical and immunologic studies in a butcher with work-related asthma. Both the positive methacholine inhalation test and the significant changes observed in PEFR measurements supported the diagnosis of asthma. The significant fall observed in PEFR measurements when the patient handled aniseed supported the diagnosis of occupational asthma. Skin prick tests carried out with 13 spices showed positive reactions only to aniseed extract. The patient had high levels of specific antianiseed IgE antibodies. The bronchial challenge test with an aniseed extract showed an immediate response without a late response. These findings suggest that the respiratory symptoms in our patient were induced by the inhalation of aniseed dust through an IgE-mediated immunologic mechanism of immediate hypersensitivity. This study established the diagnosis of occupational asthma from aniseed dust sensitization.

Cross-reactivity between quinolones. Report of three cases.

Cross-reactivity between quinolones is uncertain. Recently, we studied three patients who had developed suspected allergic reactions to a quinolone. For all of them we performed skin test, histamine release test, RAST, and oral provocation with the suspected quinolone and also with another quinolone of the opposite generation. Five atopic and five nonatopic subjects were used as controls. Neither skin test, histamine release test, nor RAST was useful in the diagnosis. By means of oral controlled provocation, the reactions were reproduced, and all the patients also reacted to another quinolone. We concluded that cross-reactivity between quinolones seems to be very important, and avoidance of any quinolone should be recommended to any patient who has suffered an allergic reaction to one of these drugs.

Specific IgE antibody response to human insulin in diabetic subjects.

Treatment with heterologous insulin preparations induce insulin antibody formation in most of the patients. A hundred of diabetic individuals in treatment with human insulin (HI) for at least 6 months at the time of the study and without any clinical immunological reaction, were selected in order to study the development of specific IgE antibodies against HI by in vivo and in vitro methods. Serologic specific IgE antibodies to HI were measured by RAST (Pharmacia) and 5 RAST-positive subjects were found. The specificity of these results were confirmed in 4 of the 5 subjects by RAST-inhibition. Thus, the prevalence of specific serologic IgE to HI in our study was 4% (1.1%-9.9%, p < 0.05). Only two of the RAST-positive subjects had cutaneous reactivity to HI by intradermal technique and one of the RAST-negative subjects presented also insulin skin reactivity. HI skin reactivity was found in 3% (0.6%-8.5%, p < 0.05) of the 100 diabetic subjects. These results differ from others obtained with heterologous insulins.

Recurrent pericarditis: a rare complication of allergen immunotherapy.

We report on a 29-year-old woman suffering from hay fever due to grass and olive tree pollens. She developed recurrent pericarditis during her first course of immunotherapy with an alum-adsorbed pollen extract. A causal relationship was established between the allergen injections and the acute pericarditis episodes on two consecutive occasions, which presented with blood eosinophilia. Blood cultures and serological tests for microorganisms were negative. There were no signs of autoimmune disease or systemic vasculitis. To the best of our knowledge, allergen immunotherapy-induced pericarditis has not been previously reported.

Allergy to cefazolin: study of in vivo cross reactivity with other betalactams.

We present two cases of hypersensitivity to cefazolin (one anaphylaxis). The skin prick tests with cefazolin at therapeutic concentration were positive. For the in vitro study we used conjugates of cefazolin with human serum albumin, obtaining a positive result in the histamine release test in both patients. In one case, we demonstrated anticefazolin-specific IgE antibodies by RAST. The controls did not react to any of these tests. Finally, we carried out skin tests and challenge tests with other betalactam antibiotics, including benzylpenicillin, amoxicillin, aztreonam, cefuroxime and cefotaxime, showing in both patients good tolerance to all these drugs.

Immediate allergy to natural latex: clinical and immunological studies.

Since 1979 several reports of contact urticaria due to natural latex have been documented. In recent years cases of anaphylaxis, rhinitis, and asthma due to latex have appeared. Nine patients, studied in our clinic between 1986-1991, suffered immediate allergic reactions caused by rubber products. All showed an immediate skin reaction to latex extract. Rub testing with surgical gloves was positive in eight patients. Immunological techniques (RAST, ELISA, HRT) demonstrated specific IgE against latex. Specific bronchial provocation testing was performed in one patient who presented with asthma when she used latex surgical gloves. Patch testing to common rubber additives were negative in our patients. These results suggest that natural latex antigens present in rubber objects can cause hypersensitivity reactions probably due to IgE-mediated mechanisms.

Allergy to amoxicillin in patients who tolerated benzylpenicillin, aztreonam, and ceftazidime.

The usual battery of skin tests employed for determining penicillin allergy may fail to detect allergic reactions to side chain-specific beta-lactam agents. We report the cases of six patients who experienced anaphylactic reactions after treatment and challenge with amoxicillin but who tolerated parenteral challenges with benzylpenicillin, aztreonam, and ceftazidime. Results of skin tests for amoxicillin (10 mg/mL) were positive for four of the six patients.

Swiss chard hypersensitivity: clinical and immunologic study.

Allergy to vegetables and fruits seems to be more prevalent in atopics, especially in birch pollen-sensitized individuals. We report a case of a grass pollen-sensitized woman, in whom the inhalation of vapor from boiling Swiss chard precipitated rhinoconjunctivitis and asthma. Type I hypersensitivity to Swiss chard was demonstrated by means of immediate skin test reactivity, specific IgE determination by RAST, basophil degranulation, histamine release test, and an immediate bronchial provocation test response to Swiss chard extract. The controls did not react to any of these tests. RAST inhibition assays suggest the presence of some cross-reactivity among Swiss chard and grass pollen antigens, as well as cross-reactivity between vegetables and weed pollens of the chenopod family.

Occupational asthma due to latex surgical gloves.

Since 1979 several reports of contact urticaria due to natural latex have been well documented. Recent case reports suggest that rhinitis and asthma may also be due to rubber exposure. We describe an operating room nurse who was exposed at work to natural rubber (latex) due to the use of latex surgical gloves. After 25 years, she developed contact urticaria, rhinoconjunctivitis and acute asthma following the handling of rubber gloves for surgical purposes. She was symptom-free when on vacation. Skin prick testing demonstrated an immediate skin reaction to latex. Rub testing with surgical gloves was positive. Specific IgE antibodies to latex were found by indirect ELISA. Specific bronchial challenge with latex extract elicited an isolated immediate asthmatic reaction that was inhibited with cromolyn sodium pretreatment. Patch testing to common rubber additives was negative. These results suggest that latex present in surgical rubber gloves and probably acting as inhalant allergen may produce occupational asthma in exposed subjects, probably by means of an IgE-mediated mechanism.