Objective: To evaluate the viability of sputum cytology in asthmatic children, recognizing inflammatory patterns and correlating them with clinical, epidemiological and functional variables of the disease. Methods: This was a cross-sectional and observational study of children with asthma who underwent sputum induction through increasing concentrations of nebulized hypertonic saline solution from 3% to 7%. The samples were processed according to the technique developed by Pizzichini et al. and the cytological pattern classified as pauci-granulocytic, neutrophilic, eosinophilic and mixed. Samples with cell viability> 50% were considered adequate. Asthma control was assessed using the asthma control test (ACT). Results: Seventy-nine children performed sputum induction. Thirty-three samples were excluded because they were not viable for analysis, resulting in 46 samples. The children’s average age was 9.4 (± 3) years. There was a predominance of eosinophilic (25/46, 54.3%), followed by mixed (13/46, 28.3%), pauci-granulocytic (7/46, 15.2%) and neutrophilic (1/46, 2.2%) pattern. Sixty-three percent of the children had severe asthma and 84.7% were treated with inhaled corticosteroids. The ACT showed that 25 (56.8%) patients had the disease under control. Forty-five children (97.8%) underwent pulmonary function tests (spirometry) and in 13 cases (28.9%) an obstructive ventilatory defect was found. Conclusions: The eosinophilic profile was predominant in the assessed asthmatic children. Non-eosinophilic phenotypes were found, but less frequently. There was no difference between the clinical variables and the sputum profile in this study group. Sputum induction in children with asthma is feasible and safe and can contribute to a specific and personalized approach to the disease.

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Manuscript title: Do gender and puberty influence allergic diseases?To the Editor:The differences between biological sex, gender identity and its impact on health can have significant implications for the prevention, screening, diagnosis and treatment of various diseases, including allergic diseases. Gender and sex are multidimensional, interactive, intertwined and are sometimes difficult to separate, so the use of the two words (gender and sex) can help to understand the social, cultural and biological context.1During childhood (0-10 years) prevalence of allergic rhinitis (AR) is higher among boys than girls. On the contrary, during adolescence (11-17 years) females display higher prevalence of AR compared to their male counterparts. However, when they reach adulthood (18-79 years), there is no difference in prevalence between genders. The same pattern occurs, even more pronounced, for prevalence of coexisting AR and asthma.2,3In the first year of life, rates of allergic sensitization (specific IgE production) are significantly higher in males, as are serum levels of total IgE. In this age group, serum levels of total IgE appear to suffer a strong genetic influence and may not predict levels of total IgE in the same individual later in life. Increased levels of IgE and higher prevalence of sensitization in boys remains until adolescence. After puberty, total serum and allergen-specific IgE levels in men are thought to remain higher or comparable to those in women. In adulthood, IgE levels decrease in both genders. In addition to changes during life, IgE levels are also influenced by menstrual periods and pregnancy, suggesting the participation of sex hormones in their regulation.4A recent analysis performed in 4,500 brazilian children aged 13-14 years has shown that females not only have a higher prevalence of AR compared to males, but also of allergic rhinoconjunctivitis (ARC), asthma, allergic conjunctivitis (AC) and atopic dermatitis (AD) (Figure 1, A). Interestingly, there is an opposite allergic sensitization pattern with respect to gender, with more allergic sensitization in boys than in girls (Figure 1, B). Moreover, it has also been observed that monosensitization is more frequent in females, while polysensitization is more common in males.5A global meta-analysis showed sex-related differences in rhinitis prevalence with a switch at around puberty from a male predominance to a female predominance. For the prevalence of rhinitis in adulthood, this evaluation found no predominance in either males or females, although the number of studies was low. In the future, it will be mandatory to perform longitudinal studies in which the follow-up is continued into adulthood.6A meta-analysis of longitudinal birth cohorts showed a sex shift from higher incidence in boys before puberty towards a rather sex-balanced incidence after puberty onset. The elevated risk of asthma and rhinitis incidences in teenage girls should lead to more consideration of a sex-specific and age-specific focus on diagnosis and treatment of respiratory diseases.7The complexity of most allergic diseases is based on a dynamic heterogeneous combination of hyperresponsiveness, dysregulated immune response, chronic inflammation, and tissue remodeling in affected organs. It is vital to systematically investigate sex disparities, possibly in different age groups, allergic diseases incidence, and their outcomes. When they are identified, it is necessary to elucidate their biological basis and understand if better outcomes could be obtained with sex-specific treatment modifications.8There are different risk factors for developing allergic diseases in boys and girls. A longitudinal study found that obesity, together with rhinitis and current smoking were risk factors for developing asthma in girls, while the main risk factors for boys were reduced FEV1, seasonal allergic symptoms and a family history of asthma.9To optimize clinical practice, it is necessary to understand, in addition to the molecular mechanisms and biomarkers, the phenotypes of allergic diseases, as well as the difference in their distribution between genders. This is recognized as an innovative element, as there is scientific evidence that men and women not only have distinct clinical manifestations for the same disease, but have different therapeutic responses. These can be influenced by biological (hormonal, organic) and socio-cultural factors (adherence to treatment, work, purchasing power).8Men and women have different lifestyles, in terms of choosing specific professions, sports, intake of hormonal medications and quality of diet. Immune cells (lymphocytes, monocytes, eosinophils and mast cells) express hormone receptors and, therefore, may be highly influenced by endogenous and exogenous hormones, which fluctuate in women.1Longitudinal studies would be interesting to evaluate possible mechanisms underlying these differences in prevalence. Sex- and gender-specific evaluations beyond 14 years of age are scarce and further allergic multimorbidity studies in different populations, especially in adults, are necessary.3 References:Franconi F, Campesi I, Colombo D, Antonini P. Sex-Gender variable: methodological recommendations for increasing scientific value of clinical studies. Cells. 2019;8(5):476. doi: 10.3390/cells8050476Keller T, Hohmann C, Standi M, Wijga AH, Gehring U, Melén E, et al. The sex-shift in single disease and multimorbid asthma and rhinitis during puberty – a study by MeDALL. Allergy. 2018;73(3):602-614. doi: 10.1111/all.13312Frohlich M, Pinart Gilberga M, Keller T, Reich A, Cabieses B, Hohmann C, et al. Is there a sex-shift in prevalence of allergic rhinitis and comorbid asthma from childhood to adulthood? A meta-analysis. Clin Transl Allergy. 2017;7:44. doi: 10.1186/s13601-017-0176-5Leffler J, Stumbles PA, Strickland DH. Immunological Processes Driving IgE Sensitisation and Disease Development in Males and Females. Int J Mol Sci. 2018;19:1554. doi: 10.3390/ijms19061554Rosario CS. Fatores associados à conjuntivite alérgica em adolescents de Curitiba, Paraná. [Dissertação] 2018. Curitiba (PR): Universidade Federal do Paraná. https://hdl.handle.net/1884/65989 (2018). Accessed 14 Apr 2020.Pinart M, Keller T, Reich A, Fröhlich M, Cabieses B, Hohmann C, et al. Sex-related allergic rhinitis prevalence switch from childhood to adulthood: a systematic review and meta-analysis. Int Arch Allergy Immunol. 2017;172(4):224-235. doi: 10.1159/000464324Hohmann C, Keller T, Gehring U, Wijga A, Standi M, Kull I, et al. Sex-specific incidence of asthma, rhinitis and respiratory multimorbidity before and after puberty onset: individual participant meta-analysis of five birth cohorts collaborating in MeDALL. BMJ Open Respir Res. 2019 doi:10.1136/ bmjresp-2019-000460De Martinis M, Sirufo MM, Suppa M, Di Silvestre D, Ginaldi L. Sex and gender aspects for patient stratification in allergy prevention and treatment. Int J Mol Sci. 2020;21(4):1535. https://doi.org/10.1016/j.jaip.2018.08.008Kalm-Stephens P, Nordvall L, Janson C, Neuman A, Malinovschi A, Alving K. Different baseline characteristics are associated with incident wheeze in female and male adolescents. Acta Paediatr. 2020 Mar 18. doi: 10.1111/apa.15263 [epub ahead of print].Rosario CS1, Cardozo CA2, Chong Neto HJ1, Rosario NA1,1-Pediatric Allergy and Immunology, Federal University of Parana.2- Department of Pediatrics, Universidade Positivo.Cristine Secco Rosário: ORCID ID https://orcid.org/0000-0003-4457-3540 [email protected] Alves Cardozo: ORCID ID [email protected] 0000-0001-6091-7142Herberto José Chong Neto: ORCID ID [email protected] https://orcid.org/0000-0002-7960-3925Nelson Augusto Rosário: ORCID ID https://orcid.org/0000-0002-8550-8051 [email protected] author: Cristine Secco Rosário. Address: Rua Padre Camargo, 453. Alto da Gloria. Curitiba – PR – Brazil. Tel: +55 (41) 3208-6500. e-mail: [email protected]