Are changes in antibiotic prophylaxis recommendations responsible for an increased risk of cefazolin allergy?

BACKGROUND: The first line of prevention of surgical site infection relies on the timely administration of antibiotic prophylaxis. First- and second-generation cephalosporins are the most recommended antibiotics in elective surgery. The incidence of cefazolin allergy has increased worldwide over the years. The sensitization mechanism of cefazolin is currently unknown, and data supporting cross-reactivity between penicillins and cephalosporins are lacking. Sensitization could occur through previous exposure either to cefazolin or to structurally related chemical agents. The objective of this study was to evaluate sensitization agents towards cefazolin. METHODS: The OpenBabel chemoinformatics toolbox was used to search for similarities between cefazolin and other molecules in an extensive drug database. Using the pholcodine-rocuronium similarity score as a threshold, we selected drugs with the most similar structure to that of cefazolin. Exposure to those drugs and cefazolin was assessed in a cohort of patients with skin test-proven cefazolin allergy at a specialized allergy centre via a self-administered anonymous questionnaire. RESULTS: Using the pholcodine-rocuronium similarity score as a threshold (score≥0.7), 42 molecules were found to be similar to cefazolin (all cephalosporins). Only 8 were marketed in France. None of the 14 cefazolin-allergic patients who answered the questionnaire (65% female, median age 56 years) reported exposure to any identified antibiotics. In contrast, 11 (78%) had at least one previous surgery requiring cefazolin before the index case. CONCLUSION: Direct previous cefazolin exposure was identified in 78% of cefazolin-allergic patients. Cefazolin started to take a central place in antibiotic prophylaxis after 2010, when cefamandole usage decreased drastically. Changes in antibiotic prophylaxis over the past 14 years in France could have been the turning point for the increased incidence of cefazolin allergy.

[Environmental risk factors for asthma developement]. / Facteurs environnementaux favorisant le développement d'un asthme.

The prevalence of asthma has increased rapidly since the early 1970s, and only changes in exposure to environmental factors; which go together with changes in lifestyle, are likely to explain such a rapid increase. Exposure to allergens is a risk factor for allergic sensitization, and allergic sensitization is a risk factor for allergic asthma. However, apart from indoor mold exposure as a risk factor for childhood asthma, there is insufficient evidence to conclude that the associations between allergen exposure and asthma development are causal. A new challenge for research is to analyze the huge amount of data derived from the metagenomic characterization of the environmental and human microbiome, to understand the role of interactions between viruses, bacteria and allergens in the development of asthma. It is recognized that prenatal and postnatal exposure to air pollution and maternal smoking increase the risk of developing asthma in children. In adults, the data are scarce and the results remain controversial as regards these exposures and asthma incidence. Further research is needed to appraise the effect of exposure to phenols, phthalates and perfluorinated compounds, which are widespread in the environment and may be associated with asthma, especially in children. Frequent use of chemicals for home cleaning especially in the form of sprays - which is a common practice at the population level - is a risk factor for the development of adult asthma. The domestic use of cleaning products might also be a risk factor for asthma in children exposed at home. The chemicals involved in these relationships are still to be identified. Occupational asthma is a major phenotype of adult asthma. A significant part of these asthma cases might relate to occupational exposure to cleaning products. While there is evidence of associations between diet during pregnancy or during childhood and the risk of developing asthma in children, the data in adults are insufficient. Beyond genetic factors, body composition is influenced by dietary choices and physical activity. Further research is needed to clarify the complex interplay between these nutritional factors and asthma development. The new challenge for research is to decipher the role of all the environmental factors to which the individual is exposed since conception ("exposome") in the development of asthma, using a holistic approach.

Smoking, telomere length and lung function decline: a longitudinal population-based study.

Telomere shortening is associated with COPD and impaired lung function in cross-sectional studies, but there is no longitudinal study. We used data from 448 participants recruited as part of the French follow-up of the European Community Respiratory Health Survey. We found no relationship between telomere length at baseline and FEV1 decline after 11 years of follow-up. However, heavy smoking was associated with an accelerated FEV1 decline in individuals with short telomeres, but not in subjects with longer telomeres (p for interaction p=0.08). Our findings suggest that short telomere length in peripheral leucocytes might be a marker for increased susceptibility to the effect of smoking.

Rhinitis and onset of asthma: a longitudinal population-based study.

BACKGROUND: A close relation between asthma and allergic rhinitis has been reported by several epidemiological and clinical studies. However, the nature of this relation remains unclear. We used the follow-up data from the European Community Respiratory Health Survey to investigate the onset of asthma in patients with allergic and non-allergic rhinitis during an 8.8-year period. METHODS: We did a longitudinal population-based study, which included 29 centres (14 countries) mostly in western Europe. Frequency of asthma was studied in 6461 participants, aged 20-44 years, without asthma at baseline. Incident asthma was defined as reporting ever having had asthma confirmed by a physician between the two surveys. Atopy was defined as a positive skin-prick test to mites, cat, Alternaria, Cladosporium, grass, birch, Parietaria, olive, or ragweed. Participants were classified into four groups at baseline: controls (no atopy, no rhinitis; n=3163), atopy only (atopy, no rhinitis; n=704), non-allergic rhinitis (rhinitis, no atopy; n=1377), and allergic rhinitis (atopy+rhinitis; n=1217). Cox proportional hazards models were used to study asthma onset in the four groups. FINDINGS: The 8.8-year cumulative incidence of asthma was 2.2% (140 events), and was different in the four groups (1.1% (36), 1.9% (13), 3.1% (42), and 4.0% (49), respectively; p<0.0001). After controlling for country, sex, baseline age, body-mass index, forced expiratory volume in 1 s (FEV(1)), log total IgE, family history of asthma, and smoking, the adjusted relative risk for asthma was 1.63 (95% CI 0.82-3.24) for atopy only, 2.71 (1.64-4.46) for non-allergic rhinitis, and 3.53 (2.11-5.91) for allergic rhinitis. Only allergic rhinitis with sensitisation to mite was associated with increased risk of asthma independently of other allergens (2.79 [1.57-4.96]). INTERPRETATION: Rhinitis, even in the absence of atopy, is a powerful predictor of adult-onset asthma.

Effect of formaldehyde on asthmatic response to inhaled allergen challenge.

BACKGROUND: Exposure to formaldehyde may lead to exacerbation of asthma. OBJECTIVES: Our aim in this study was to investigate whether exposure to a low level (500 microg/m(3)) of formaldehyde enhances inhaled allergen responses. METHODS: Twelve subjects with intermittent asthma and allergy to pollen were exposed, at rest, in a double-blind crossover study to either formaldehyde or purified air for 60 min. The order of exposure to formaldehyde and air-only was randomized, and exposures were separated by 2 weeks. We also performed an allergen inhalation challenge after each exposure. Airway responsiveness to methacholine and lower airway inflammation (induced sputum) were assessed 8 hr after allergen challenge. RESULTS: The median dose of allergen producing a 15% decrease in forced expiratory volume in 1 sec (PD(15)FEV(1)) was 0.80 IR (index of reactivity) after formaldehyde exposure compared with 0.25 IR after air-only exposure (p = 0.06). Formaldehyde exposure did not affect allergen-induced increase in responsiveness to methacholine (p = 0.42). We found no formaldehyde-associated effect on the airway inflammatory response, in particular the eosinophilic inflammatory response, induced by the allergen challenge 8 hr before. CONCLUSION: In this study, exposure to 500 microg/m(3) formaldehyde had no significant deleterious effect on airway allergen responsiveness of patients with intermittent asthma; we found a trend toward a protective effect.

Dramatic effect of sirolimus on renal angiomyolipomas in a patient with tuberous sclerosis complex.

Angiomyolipomas are very common in patients with tuberous sclerosis complex (TSC) and cause substantial morbidity. Until now, arterial embolization has been the recommended treatment for symptomatic patients. We report the case of a woman with TSC and giant angiolipomas in whom sirolimus induced a dramatic reduction in bilateral renal tumors.

Bronchial hyperresponsiveness to methacholine is associated with increased common carotid intima-media thickness in men.

BACKGROUND: Respiratory alterations have been associated with subsequent coronary heart diseases in numerous population-based studies. The underlying mechanisms remain largely unknown. The objective of this study was to examine the association between bronchial hyperresponsiveness (BHR) to methacholine (which reflects local inflammation in the bronchus) and common carotid intima-media thickness (CCA-IMT). METHODS AND RESULTS: As part of the European Community Respiratory Health Survey follow-up, in Paris Center, we assessed BHR to methacholine (> or =20% decrease in FEV1 for a maximum methacholine dose of 4 mg) and measured CCA-IMT by ultrasonography in 255 adults free of cardiovascular diseases aged 29 to 56 years (123 men, 132 women; mean age 44.5 years, 43.5% never smokers). In men, CCA-IMT mean value was higher in subjects with BHR than in those without (0.68+/-0.11 versus 0.62+/-0.09 mm, P=0.002). No association was found in women. Multivariate analysis confirmed the independent association between BHR and CCA-IMT in men (adjusted odds ratio for a 0.10-mm increase in CCA-IMT=2.1, 95% confidence interval: 1.1 to 4.3; P=0.02). These results remained similar after exclusion of asthmatic subjects (n=11). In each strata of smoking status (nonsmoker, ex-smoker, and current smokers), CCA-IMT mean values tended to be higher in subjects with BHR than in those without, although the difference between the 2 groups was more pronounced in current smokers. CONCLUSIONS: The results of the present study suggest that BHR is independently associated with CCA-IMT in men. The interrelationships between cardiovascular and respiratory alterations should be further investigated.