Sputum eosinophilia is a determinant of FEV1 decline in occupational asthma: results of an observational study

Juan Carlos Ivancevich Saturday, 10 January 2015 14:59

Talini D1Novelli F2Bacci E2Bartoli M2Cianchetti S2Costa F2Dente FL2Di Franco A2Latorre M2Malagrinò L2Vagaggini B2Celi A2Paggiaro P2.



To evaluate the potential determinants of forced expiratory volume in 1 s (FEV1) decline in workers with occupational asthma (OA) still exposed to the causative agent. We hypothesised that sputum eosinophilia might be a predictor of poor asthma outcome after diagnosis.


In a specialistic clinical centre of the University Hospital of Pisa, we studied 39 participants (28 M, 11 F) diagnosed as having OA, routinely followed up between 1990 and 2009. They were a subgroup of 94 participants diagnosed as affected by OA in that period: 9 had been removed from work at the diagnosis, 21 were excluded for having ceased occupational exposure after few months from diagnosis, and 25 were lost at the follow-up or had no acceptable sputum measurements at the diagnosis. Estimates of the decline in FEV1 were obtained by means of simple regression analysis during the period of occupational exposure after diagnosis. Logistic regression was used to analyse the effects of factors (baseline FEV1 and sputum inflammatory cells, duration and type of exposure) that may potentially influence FEV1 decline.


At follow-up (5.7+3.7 years), most participants were still symptomatic despite inhaled corticosteroids (ICS) treatment and had their occupational exposure reduced. Participants with higher sputum eosinophils (>3%) at baseline had a significantly greater decline of FEV1 (-52.5 vs -18.6 mL/year, p=0.012). Logistic regression showed that persistent exposure and sputum eosinophilia were significantly associated with a greater decline in FEV1 (OR 11.5, 95% CI 1.8 to 71.4, p=0.009 and OR 6.7, 95% CI 1.1 to 41.7, p= 0.042, respectively).


Sputum eosinophilia at diagnosis, together with the persistence of occupational exposure during follow-up, may contribute to a greater decline in FEV1 in patients with OA still at work. Further long-term studies are required as to whether intensive ICS treatment may be beneficial for patients with OA and increase ad eosinophilic inflammation.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

This Article

Occupational exposures, smoking and airway inflammation in refractory asthma

Juan Carlos Ivancevich Monday, 05 January 2015 03:41
Open Access
Research article

Jodie L SimpsonMaya GuestMay M Boggess and Peter G Gibson

BMC Pulmonary Medicine 2014, 14:207  doi:10.1186/1471-2466-14-207

Published: 19 December 2014

Abstract (provisional)


The influence of occupation and ex/passive smoking on inflammatory phenotype is not well understood. The aim of this study was to examine the relationship between occupation, past smoking and current passive smoking and airway inflammation in a population of adults with refractory asthma.


Sixty-six participants with refractory asthma were characterised. Occupational exposure to asthma causing or worsening agents were identified with an asthma-specific job exposure matrix. Exposure to passive cigarette smoke was determined by questionnaire and exhaled carbon monoxide assessment. The carbon content of macrophages was assessed in a sub-group of participants.


Nineteen participants had smoked previously with low smoking pack years (median 1.7 years). Ex-smokers more commonly lived with a current smoker (26% vs. 9%, p = 0.11) and were more likely to allow smoking inside their home (26% vs. 4%, p = 0.02) compared to never smokers. Twenty participants had occupations with an identified exposure risk to an asthmagen; thirteen had exposures to irritants such as motor vehicle exhaust and environmental tobacco smoke. Sputum neutrophils were elevated in participants with asthma who had occupational exposures, particularly those who were diagnosed with asthma at a more than 30 years of age.


Sputum neutrophils are elevated in refractory asthma with exposure to occupational asthmagens. In addition to older age, exposure to both environmental and occupational particulate matter may contribute to the presence of neutrophilic asthma. This may help explain asthma heterogeneity and geographical variations in airway inflammatory phenotypes in asthma.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

Pathophysiological characterization of asthma transitions across adolescence

Juan Carlos Ivancevich Monday, 15 December 2014 14:49
Open Access

Syed Hasan Arshad123*Abid Raza1Laurie Lau2Khalid Bawakid2Wilfried Karmaus4,Hongmei Zhang4Susan Ewart5Veersh Patil1Graham Roberts123 and Ramesh Kurukulaaratchy123

  • *Corresponding author: Syed H Arshad This email address is being protected from spambots. You need JavaScript enabled to view it.

Author Affiliations



Adolescence is a period of change, which coincides with disease remission in a significant proportion of subjects with childhood asthma. There is incomplete understanding of the changing characteristics underlying different adolescent asthma transitions. We undertook pathophysiological characterization of transitional adolescent asthma phenotypes in a longitudinal birth cohort.


The Isle of Wight Birth Cohort (N = 1456) was reviewed at 1, 2, 4, 10 and 18-years. Characterization included questionnaires, skin tests, spirometry, exhaled nitric oxide, bronchial challenge and (in a subset of 100 at 18-years) induced sputum. Asthma groups were “never asthma” (no asthma since birth), “persistent asthma” (asthma at age 10 and 18), “remission asthma” (asthma at age 10 but not at 18) and “adolescent-onset asthma” (asthma at age 18 but not at age 10).


Participants whose asthma remitted during adolescence had lower bronchial reactivity (odds ratio (OR) 0.30; CI 0.10 -0.90; p = 0.03) at age 10 plus greater improvement in lung function (forced expiratory flow 25-75% gain: 1.7 L; 1.0-2.9; p = 0.04) compared to persistent asthma by age 18. Male sex (0.3; 0.1-0.7; p < 0.01) and lower acetaminophen use (0.4; 0.2-0.8; p < 0.01) independently favoured asthma remission, when compared to persistent asthma. Asthma remission had a lower total sputum cell count compared to never asthma (31.5 [25–75 centiles] 12.9-40.4) vs. 47.0 (19.5-181.3); p = 0.03). Sputum examination in adolescent-onset asthma showed eosinophilic airway inflammation (3.0%, 0.7-6.6), not seen in persistent asthma (1.0%, 0–3.9), while remission group had the lowest sputum eosinophil count (0.3%, 0–1.4) and lowest eosinophils/neutrophils ratio of 0.0 (Interquartile range: 0.1).


Asthma remission during adolescence is associated with lower initial BHR and greater gain in small airways function, while adolescent-onset asthma is primarily eosinophilic.

Distribution of airway smooth muscle remodelling in asthma: Relation to airway inflammation

Juan Carlos Ivancevich Wednesday, 17 December 2014 14:03


Volume 20Issue 1pages 66–72January 2015

  1. John G. Elliot1
  2. Robyn L. Jones1
  3. Michael J. Abramson3
  4. Francis H. Green6
  5. Thais Mauad8
  6. Karen O. McKay4,5
  7. Tony R. Bai7and
  8. Alan L. James1,2,*

DOI: 10.1111/resp.12384


Background and objective: Pathological phenotypes of asthma have been based predominantly on inflammation, rather than airway wall remodelling. Differences in the distribution of airway smooth muscle (ASM) remodelling between large and small airways may affect clinical outcomes in asthma. The aim of this study was to examine the distribution of ASM remodelling and its relation to airway inflammation.

Methods: Post-mortem cases of asthma (n = 68) were categorized by the distribution of increased thickness of the ASM layer (relative to nonasthmatic controls, n = 37), into ‘large only’ (LO, n = 15), ‘small only’ (SO, n = 4) ‘large/small’ (LS, n = 24) or no increase (NI, n = 25). Subject characteristics, ASM and airway wall dimensions and inflammatory cell numbers were compared between groups.

Results. Apart from reduced clinical severity of asthma in NI cases (P = 0.002), subject characteristics did not distinguish asthma groups. Compared with control subjects, ASM cell number, reticular basement membrane thickness, airway wall thickness, percent muscle shortening and eosinophil number were increased (P < 0.05) in both large and small airways in LS cases and only the large airways in LO cases. Increased numbers of neutrophils were observed only in the small airways of LO cases.

Conclusions: Distinct distributions of ASM remodelling are seen in asthma. Pathology limited to the small airways was uncommon. Increased thickness of the ASM layer was associated with airway remodelling and eosinophilia, but not neutrophilia. These data support the presence of distinct pathological phenotypes based on the site of increased ASM.

Use of digital media for the education of health professionals in the treatment of childhood asthma

Juan Carlos Ivancevich Thursday, 11 December 2014 18:33



Inhalation therapy is the main treatment for asthma and its adequate use has been a factor responsible for disease control; therefore, the aim of the study was to determine whether a digital media tool, which features portability on mobile phones, modifies the assimilation of the inhalation technique.


A total of 66 professionals working in the health care area with the pediatric population were selected. They were submitted to a pre-test on their knowledge of inhalation therapy. The professionals were randomized into two groups (A and B). Group A received a media application on their mobile phones showing the steps of inhalation therapy, while group B received the same information in written form only. A post-test was applied after 15 days. The results (pre- and post-) were analyzed by two pediatric pulmonologists.


Of the 66 professionals, 87.9% were females. Of a total possible score of ten, the mean score obtained in the pre-test was 5.3 ± 3, and in the second test, 7.5 ± 2 (p < 0.000). There were no significant differences when comparing the two groups (p = 0.726). The nurses had the lowest mean scores in the initial test (2.3 ± 2); however, they were the group that learned the most with the intervention, showing similar means to those of other groups in the second test (6.1 ± 3).


There was significant improvement in knowledge about inhalation therapy in all professional categories using both methods, demonstrating that education, when available to professionals, positively modifies medical practice.



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