Gianna Moscato

Noninvasive methods for assessment of airway inflammation in occupational settings

To cite this article: Quirce S, Lemière C, de Blay F, del Pozo V, Gerth Van Wijk R, Maestrelli P, Pauli G, Pignatti P, Raulf‐Heimsoth M, Sastre J, Storaas T, Moscato G. Noninvasive methods for assessment of airway inflammation in occupational settings. Allergy 2010; 65: 445–458.

Comparison between exhaled and sputum oxidative stress biomarkers in chronic airway inflammation

The aim of the present study was to compare aldehyde levels resulting from lipid peroxidation in exhaled breath condensate (EBC) and induced sputum (IS) supernatant of subjects with asthma and chronic obstructive pulmonary disease (COPD). Aldehydes (malondialdehyde (MDA), acrolein, n-hexanal (C6), n-heptanal (C7), n-nonanal (C9), 4-hydroxynonenal (HNE) and 4-hydroxyhexenal (HHE)) in both biological fluids were measured by liquid chromatography-tandem mass spectrometry. MDA concentrations in sputum were 132.5 nM (82.5–268.8) and 23.7 nM (9–53.7) in EBC. Similarly, C6, C7 and C9 concentrations in IS were 1.5–4.7-fold higher than in EBC. Acrolein levels were 131.1 nM (55.6–264.6) in IS and 45.3 nM (14.4–127.1) in EBC. The concentrations of HNE and HHE in IS were not significantly different from the levels in EBC. Aldehyde levels in EBC did not show any correlation with aldehyde levels in IS or with differential sputum cellular count. In COPD, MDA in EBC, but not its IS counterpart, was negatively correlated with the severity of disease. In conclusion, the data presented here show that aldehydes can be detected in both exhaled breath condensate and supernatant of induced sputum, but that their relative concentrations are different and not correlated with each other. Therefore, with regard to lipid peroxidation products, exhaled breath condensate and induced sputum must be considered as independent techniques.

What are the questionnaire items most useful in identifying subjects with occupational asthma

The present study assessed the usefulness of key items obtained from a clinical “open” questionnaire prospectively administered to 212 subjects, referred to four tertiary-care hospitals for predicting the diagnosis of occupational asthma (OA). Of these subjects, 72 (34%) were diagnosed as OA (53% with OA due to high-molecular-weight agents) according to results of specific inhalation challenges, and 90 (42%) as non-OA. Wheezing at work occurred in 88% of subjects with OA and was the most specific symptom (85%). Nasal and eye symptoms were commonly associated symptoms. Wheezing, nasal and ocular itching at work were positively, and loss of voice negatively associated with the presence of OA in the case of high-, but not low molecular-weight agents. A prediction model based on responses to nasal itching, daily symptoms over the week at work, nasal secretions, absence of loss of voice, wheezing, and sputum, correctly predicted 156 out of 212 (74%) subjects according to the presence or absence of OA by final diagnosis. In conclusion, key items, i.e. wheezing, nasal and ocular itching and loss of voice, are satisfactorily associated with the presence of occupational asthma in subjects exposed to high-molecular-weight agents. Therefore, these should be addressed with high priority by physicians. However, no questionnaire-derived item is helpful in subjects exposed to low-molecular-weight agents.

EAACI position paper on occupational rhinitis

The present document is the result of a consensus reached by a panel of experts from European and non-European countries on Occupational Rhinitis (OR), a disease of emerging relevance which has received little attention in comparison to occupational asthma. The document covers the main items of OR including epidemiology, diagnosis, management, socio-economic impact, preventive strategies and medicolegal issues. An operational definition and classification of OR tailored on that of occupational asthma, as well as a diagnostic algorithm based on steps allowing for different levels of diagnostic evidence are proposed. The needs for future research are pointed out. Key messages are issued for each item.

Specific inhalation challenge in the diagnosis of occupational asthma: consensus statement

This consensus statement provides practical recommendations for specific inhalation challenge (SIC) in the diagnosis of occupational asthma. They are derived from a systematic literature search, a census of active European centres, a Delphi conference and expert consensus. This article details each step of a SIC, including safety requirements, techniques for delivering agents, and methods for assessing and interpreting bronchial responses. The limitations of the procedure are also discussed. Testing should only be carried out in hospitals where physicians and healthcare professionals have appropriate expertise. Tests should always include a control challenge, a gradual increase of exposure to the suspected agent, and close monitoring of the patient during the challenge and for at least 6 h afterwards. In expert centres, excessive reactions provoked by SIC are rare. A positive response is defined by a fall in forced expiratory volume in 1 s ≥15% from baseline. Equivocal reactions can sometimes be clarified by finding changes in nonspecific bronchial responsiveness, sputum eosinophils or exhaled nitric oxide. The sensitivity and specificity of SIC are high but not easily quantified, as the method is usually used as the reference standard for the diagnosis of occupational asthma. ERS Task Force: a statement on specific inhalation challenges in the diagnosis of occupational asthma http://ow.ly/tCvFG

Bronchoalveolar lavage, sputum and exhaled clinically relevant inflammatory markers: values in healthy adults

Bronchoalveolar lavage (BAL), induced sputum and exhaled breath markers (exhaled nitric oxide and exhaled breath condensate) can each provide biological insights into the pathogenesis of respiratory disorders. Some of their biomarkers are also employed in the clinical management of patients with various respiratory diseases. In the clinical context, however, defining normal values and cut-off points is crucial. The aim of the present review is to investigate to what extent the issue of defining normal values in healthy adults has been pursued for the biomarkers with clinical value. The current authors reviewed data from literature that specifically addressed the issue of normal values from healthy adults for the four methodologies. Most studies have been performed for BAL (n = 9), sputum (n = 3) and nitric oxide (n = 3). There are no published studies for breath condensate, none of whose markers yet has clinical value. In healthy adult nonsmokers the cut-off points (mean+2sd) for biomarkers with clinical value were as follows. BAL: 16.7% lymphocytes, 2.3% neutrophils and 1.9% eosinophils; sputum: 7.7×106·mL−1 total cell count and 2.2% eosinophils; nitric oxide: 20.2 ppb. The methodologies differ concerning the quantity and characteristics of available reference data. Studies focusing on obtaining reference values from healthy individuals are still required, more evidently for the new, noninvasive methodologies.

Asthma and exposure to cleaning products – a European Academy of Allergy and Clinical Immunology task force consensus statement

Professional and domestic cleaning is associated with work‐related asthma (WRA). This position paper reviews the literature linking exposure to cleaning products and the risk of asthma and focuses on prevention. Increased risk of asthma has been shown in many epidemiological and surveillance studies, and several case reports describe the relationship between exposure to one or more cleaning agents and WRA. Cleaning sprays, bleach, ammonia, disinfectants, mixing products, and specific job tasks have been identified as specific causes and/or triggers of asthma. Because research conclusions and policy suggestions have remained unheeded by manufactures, vendors, and commercial cleaning companies, it is time for a multifaceted intervention. Possible preventive measures encompass the following: substitution of cleaning sprays, bleach, and ammonia; minimizing the use of disinfectants; avoidance of mixing products; use of respiratory protective devices; and worker education. Moreover, we suggest the education of unions, consumer, and public interest groups to encourage safer products. In addition, information activities for the general population with the purpose of improving the knowledge of professional and domestic cleaners regarding risks and available preventive measures and to promote strict collaboration between scientific communities and safety and health agencies are urgently needed.

Occupational asthma, rhinitis and urticaria due to piperacillin sodium in a pharmaceutical worker

A 28 year old man with no history of atopy was referred to our hospital for possible work-related asthma. He had been employed in the production section of a pharmaceutical company for 2 yrs, and in the last 2 months he had complained of dyspnoea, wheezing, chest tightness, symptoms of rhinitis and a cutaneous rash when exposed to powdered antibiotics. Symptoms disappeared after being transferred to the packaging section. When the subject was admitted to our department he was asymptomatic. Basal lung function tests were in the normal range. Bronchial challenges with methacholine and with ultrasonically-nebulized distilled water were negative. Skin-prick test with piperacillin sodium gave a strong positive response at a very low concentration. Specific inhalation challenge with piperacillin sodium resulted in an immediate asthmatic reaction, and also reproduced rhinitis symptoms and the cutaneous rash. A control challenge with lactose, and the specific challenge test with cefuroxime sodium (another antibiotic to which the patient was exposed at the workplace) were negative. We conclude that piperacillin sodium is an agent that can cause occupational asthma.

EAACI position paper: Irritant-induced asthma

The term irritant‐induced (occupational) asthma (IIA) has been used to denote various clinical forms of asthma related to irritant exposure at work. The causal relationship between irritant exposure(s) and the development of asthma can be substantiated by the temporal association between the onset of asthma symptoms and a single or multiple high‐level exposure(s) to irritants, whereas this relationship can only be inferred from epidemiological data for workers chronically exposed to moderate levels of irritants. Accordingly, the following clinical phenotypes should be distinguished within the wide spectrum of irritant‐related asthma: (i) definite IIA, that is acute‐onset IIA characterized by the rapid onset of asthma within a few hours after a single exposure to very high levels of irritant substances; (ii) probable IIA, that is asthma that develops in workers with multiple symptomatic high‐level exposures to irritants; and (iii) possible IIA, that is asthma occurring with a delayed‐onset after chronic exposure to moderate levels of irritants. This document prepared by a panel of experts summarizes our current knowledge on the diagnostic approach, epidemiology, pathophysiology, and management of the various phenotypes of IIA.

EAACI consensus statement for investigation of work‐related asthma in non‐specialized centres

Work‐related asthma (WRA) is a relevant problem in several countries, is cause of disability and socioeconomic consequences for both the patient and the society and is probably still underdiagnosed. A correct diagnosis is extremely important to reduce or limit the consequences of the disease. This consensus document was prepared by a EAACI Task Force consisting of an expert panel of allergologists, pneumologists and occupational physicians from different European countries. This document is not intended to address in detail the full diagnostic work‐up of WRA, nor to be a formal evidence‐based guideline. It is written to provide an operative protocol to allergologists and physicians dealing with asthma useful for identifying the subjects suspected of having WRA to address them to in‐depth investigations in a specialized centre. No evidence‐based system could be used because of the low grade of evidence of published studies in this area, and instead, ‘key messages’ or ‘suggestions’ are provided based on consensus of the expert panel members.