ABSTRACT

Objective:

To evaluate health-related quality of life in asthma patients treated at a referral center in southern Brazil, identifying differences between male and female patients, as well as to evaluate differences between the males and females in terms of asthma control, lung function, and nutritional status.

Methods:

This was a cross-sectional study involving patients ≥ 18 years of age treated at an asthma outpatient clinic. We evaluated clinical parameters, lung function, nutritional status, and quality of life.

Results:

A total of 198 patients completed the study. The mean age was 56.2 ± 14.8 years, and 81.8% were female. The proportion of patients with uncontrolled asthma was higher among females than among males (63.0% vs. 44.4%; p = 0.041). The body mass index (BMI) and percentage of body fat were higher in females than in males (30.2 ± 5.8 kg/m² vs. 26.9 ± 4.5 kg/m² and 37.4 ± 6.4% vs. 26.5 ± 7.4%; p = 0.002 and p < 0.001, respectively). Quality of life was lower in females than in males in the following domains: symptoms (3.8 ± 1.5 vs. 4.6 ± 1.7; p = 0.006); activity limitation (3.6 ± 1.3 vs. 4.4 ± 1.5; p = 0.001); emotional function (3.6 ± 1.9 vs. 4.5 ± 1.7; p = 0.014); and environmental stimuli (3.2 ± 1.6 vs. 4.3 ± 1.9; p = 0.001).

Conclusions:

Male asthma patients appear to fare better than do female asthma patients in terms of health-related quality of life, asthma control, BMI, percentage of body fat, and comorbidities.

Keywords:
Asthma; Nutritional status; Quality of life; Adult

RESUMO

Objetivo:

Avaliar a qualidade de vida relacionada à saúde em pacientes com asma tratados em um centro de referência no sul do Brasil e identificar diferenças entre homens e mulheres, além de avaliar as diferenças entre os sexos no tocante ao controle da asma, função pulmonar e estado nutricional.

Métodos:

Trata-se de um estudo transversal com pacientes com idade ≥ 18 anos tratados em um ambulatório de asma. Foram avaliados parâmetros clínicos, função pulmonar, estado nutricional e qualidade de vida.

Resultados:

Cento e noventa e oito pacientes completaram o estudo. A média de idade foi de 56,2 ± 14,8 anos, e 81,8% eram do sexo feminino. A proporção de pacientes com asma não controlada foi maior entre as mulheres que entre os homens (63,0% vs. 44,4%; p = 0,041). O índice de massa corporal (IMC) e a porcentagem de gordura corporal foram maiores nas mulheres que nos homens (30,2 ± 5,8 kg/m² vs. 26,9 ± 4,5 kg/m² e 37,4 ± 6,4% vs. 26,5 ± 7,4%; p = 0,002 e p < 0,001, respectivamente). A qualidade de vida foi menor nas mulheres que nos homens nos seguintes domínios: sintomas (3,8 ± 1,5 vs. 4,6 ± 1,7; p = 0,006); limitação das atividades (3,6 ± 1,3 vs. 4,4 ± 1,5; p = 0,001); função emocional (3,6 ± 1,9 vs. 4,5 ± 1,7; p = 0,014); estímulos ambientais (3,2 ± 1,6 vs. 4,3 ± 1,9; p = 0,001).

Conclusões:

Homens com asma aparentemente apresentam melhores resultados que mulheres com asma no que tange à qualidade de vida relacionada à saúde, controle da asma, IMC, porcentagem de gordura corporal e comorbidades.

Descritores:
Asma; Estado nutricional; Qualidade de vida; Adulto

INTRODUCTION

Asthma is a chronic inflammatory disease of the airways characterized by respiratory symptoms such as wheeze, shortness of breath, chest tightness, and cough that vary over time and in intensity, as well as by variable expiratory airflow limitation and airway hyperresponsiveness to direct or indirect stimuli. It is a prevalent disease that impairs quality of life, being a major public health problem. Asthma affects approximately 10% of adults worldwide.¹1 Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention 2016. Bethesda: GINA; 2016. The prevalence of asthma follows a characteristic age- and gender-related pattern, being highest during childhood and predominantly affecting males.²2 Gerritsen J. Airway responsiveness in teenagers is becoming sexier. Am J Respir Crit Care Med. 2008;178(4):321-2. https://doi.org/10.1164/rccm.200805-736ED
https://doi.org/10.1164/rccm.200805-736E... After puberty, the prevalence of asthma is higher in females than in males.²2 Gerritsen J. Airway responsiveness in teenagers is becoming sexier. Am J Respir Crit Care Med. 2008;178(4):321-2. https://doi.org/10.1164/rccm.200805-736ED
https://doi.org/10.1164/rccm.200805-736E... ^,33 Farha S, Asosingh K, Laskowski D, Hammel J, Dweik RA, Wiedemann HP, et al. Effects of the menstrual cycle on lung function variables in women with asthma. Am J Respir Crit Care Med. 2009;180(4):304-10. https://doi.org/10.1164/rccm.200904-0497OC
https://doi.org/10.1164/rccm.200904-0497...

Many mechanisms are involved in the clinical expression of asthma, including sex hormones, airway caliber, obesity, type of exposure, and age at onset.⁴4 Melgert BN, Ray A, Hylkema MN, Timens W, Postma DS. Are there reasons why adult asthma is more common in females? Curr Allergy Asthma Rep. 2007;7(2):143-50. https://doi.org/10.1007/s11882-007-0012-4
https://doi.org/10.1007/s11882-007-0012-... ^,55 Vink NM, Postma DS, Schouten JP, Rosmalen JG, Boezen HM. Gender differences in asthma development and remission during transition through puberty: the TRacking Adolescents' Individual Lives Survey (TRAILS) study. J Allergy Clin Immunol. 2010;126(3):498-504.e1-6. Although males and females with asthma share the common clinical features of the disease, the natural course of asthma differs between the genders. Takeda et al.⁶6 Takeda M, Tanabe M, Ito W, Ueki S, Konnno Y, Chihara M, et al. Gender difference in allergic airway remodelling and immunoglobulin production in mouse model of asthma. Respirology. 2013;18(5):797-806. https://doi.org/10.1111/resp.12078
https://doi.org/10.1111/resp.12078... suggested that sex hormones and gender differences are involved in cellular functions in airway remodeling. Several studies have reported that asthma is more prevalent and more severe in adult females. In a cross-sectional study, asthma severity was found to have increased with the body mass index (BMI), although only in females; however, the reason for this has yet to be explained.⁷7 Forte GC, Grutcki DM, Menegotto SM, Pereira RP, Dalcin Pde T. Prevalence of obesity in asthma and its relations with asthma severity and control. Rev Assoc Med Bras (1992). 2013;59(6):594-9. https://doi.org/10.1590/S0104-42302013000600014
https://doi.org/10.1590/S0104-4230201300...

8 Delgado J, Barranco P, Quirce S. Obesity and asthma. J Investig Allergol Clin Immunol. 2008;18(6):420-5.^-99 Ali Z, Ulrik CS. Obesity and asthma: a coincidence or a causal relationship? A systematic review. Respir Med. 2013;107(9):1287-300. https://doi.org/10.1016/j.rmed.2013.03.019
https://doi.org/10.1016/j.rmed.2013.03.0... Zillmer et al.¹⁰10 Zillmer LR, Gazzotti MR, Nascimento OA, Montealegre F, Fish J, Jardim JR. Gender differences in the perception of asthma and respiratory symptoms in a population sample of asthma patients in four Brazilian cities. J Bras Pneumol. 2014;40(6):591-8. https://doi.org/10.1590/S1806-37132014000600002
https://doi.org/10.1590/S1806-3713201400... noted that poorly controlled asthma and respiratory symptoms were more common in females than in males. In addition, self-reported quality of life is often worse in females than in males, probably due to dyspnea that is more severe and increased drug use.¹¹11 Wijnhoven HA, Kriegsman DM, Snoek FJ, Hesselink AE, de Haan M. Gender differences in health-related quality of life among asthma patients. The J Asthma. 2003;40(2):189-99. https://doi.org/10.1081/JAS-120017990
https://doi.org/10.1081/JAS-120017990... As a result of this clinical heterogeneity, treatment approaches need to be individualized and modified in order to maintain adequate symptom and disease control over time.¹²12 Lemanske RF Jr, Busse WW. Asthma: clinical expression and molecular mechanisms. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S95-102. https://doi.org/10.1016/j.jaci.2009.10.047
https://doi.org/10.1016/j.jaci.2009.10.0...

Although several studies have examined gender differences in asthma patients, few have investigated the impact of asthma on health-related quality of life and nutritional status.¹¹11 Wijnhoven HA, Kriegsman DM, Snoek FJ, Hesselink AE, de Haan M. Gender differences in health-related quality of life among asthma patients. The J Asthma. 2003;40(2):189-99. https://doi.org/10.1081/JAS-120017990
https://doi.org/10.1081/JAS-120017990... ^,1313 Belloch A, Perpi-á M, Martínez-Moragón E, de Diego A, Martínez-Francés M. Gender differences in health-related quality of life among patients with asthma. J Asthma. 2003;40(8):945-53. https://doi.org/10.1081/JAS-120024595
https://doi.org/10.1081/JAS-120024595... In addition, there are differences and regional disparities in disease control and clinical expression among asthma patients.¹⁴14 Dalcin PT, Menegotto DM, Zanonato A, Franciscatto L, Soliman F, Figueiredo M, et al. Factors associated with uncontrolled asthma in Porto Alegre, Brazil. Braz J Med Biol Res. 2009;42(11):1097-103. https://doi.org/10.1590/S0100-879X2009005000035
https://doi.org/10.1590/S0100-879X200900... Therefore, it is important to evaluate gender differences in different populations of adults with asthma.

The primary objective of the present study was to evaluate differences in health-related quality of life between adult males and females with asthma treated at a referral center in southern Brazil. A secondary objective was to evaluate differences in asthma control, lung function, and nutritional status between those two groups.

METHODS

In a cross-sectional study of prospectively collected data, we assessed consecutive adult patients with asthma recruited from among those treated at a referral center for asthma in southern Brazil. The study protocol was approved by the Research Ethics Committee of the Hospital de Clínicas de Porto Alegre (HCPA), located in the city of Porto Alegre, Brazil (Protocol no. 12.0103), and written informed consent was obtained from all patients.

Patients were recruited from among those treated at the HCPA asthma outpatient clinic, located in the city of Porto Alegre, Brazil. The study included patients who were 18 years of age or older and who had physician-diagnosed asthma. The diagnosis of asthma was confirmed by a member of the research team on the basis of the following criteria: symptoms of asthma, accompanied by reversible airflow obstruction (an increase of at least 12% and 200 mL in FEV₁ after administration of a short-acting β₂ agonist) or bronchial hyperresponsiveness to a bronchoconstricting agent (methacholine).¹1 Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention 2016. Bethesda: GINA; 2016.

The exclusion criteria were as follows: chronic lung diseases other than asthma (such as COPD and bronchiectasis); lobectomy; abnormal chest X-ray findings; pregnancy; and current or past smoking (a smoking history of more than 10 pack-years).

During an outpatient visit, participants underwent a comprehensive clinical evaluation and completed questionnaires regarding the following: medical history; socioeconomic status; demographic characteristics; smoking history; chronic comorbidities; medication use; menopause (no menstruation in the last 12 months); nutritional status; asthma severity; level of asthma control; and health-related quality of life.

Nutritional status was assessed by the body mass index (BMI), which was calculated by the formula weight/height² (kg/m²). On the basis of their BMI, participants were stratified into the following categories¹⁵15 World Health Organization. Obesity: preventing and managing the global epidemic. Report of a World Health Organization Consultation. Geneva: World Health Organization; 2000. p. 256.: underweight (< 18.5 kg/m²); normal weight (18.5-24.9 kg/m²); overweight (25-29.9 kg/m²); and obese (≥ 30 kg/m²). Bioelectrical impedance analysis was used in order to assess body composition (i.e., the proportions of muscle, fat, and water).¹⁶16 Pollock ML, Wilmore JH. Exercícios na Saúde e na Doença: Avaliação e Prescrição para Prevenção e Reabilitação. 2nd ed. Rio de Janeiro: MEDSI; 1993.

Asthma severity was determined in accordance with the Global Initiative for Asthma (GINA) guidelines,¹1 Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention 2016. Bethesda: GINA; 2016. patients being classified as having mild intermittent asthma, mild persistent asthma, moderate persistent asthma, or severe persistent asthma on the basis of daily medication use. The level of asthma control was also determined in accordance with the GINA guidelines,¹1 Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention 2016. Bethesda: GINA; 2016. patients being classified as having well-controlled, partly controlled, or uncontrolled asthma on the basis of the following: frequency of daytime and nighttime symptoms; rescue medication use; limitation of daily physical activity; and number of exacerbations in the last 4 weeks.

Spirometry was performed with a v4.31a spirometer (Jaeger, Würzburg, Germany). FVC, FEV₁, and the FEV₁/FVC ratio were measured three times, the best of the three measurements being recorded. All pulmonary function test results were expressed as a percentage of the predicted values for age, height, and gender.¹⁷17 Pereira CA, Barreto SP, Simões JG, Pereira FW, Gerstler JG, Nakatani J. Valores de referência para espirometria em uma amostra da população brasileira adulta. J Pneumol. 1992;18(1):10-22.

Quality of life was assessed by the Asthma Quality of Life Questionnaire (AQLQ),¹⁸18 Juniper EF. Health-related quality of life in asthma. Curr Opin Pulm Med. 2003;9 Suppl 1:S8-10. https://doi.org/10.1097/00063198-200304001-00003
https://doi.org/10.1097/00063198-2003040... which had previously been translated to Portuguese and validated for use in Brazil.¹⁹19 Silva LM, Silva LL. Validação do questionário de qualidade de vida em asma (Juniper) para o português brasileiro. Rev AMRGS. 2007;51(1):31-7. The AQLQ is divided into four domains: symptoms; activity limitation; emotional function; and environmental stimuli. Each domain is scored from 1 to 7, a score of 1 indicating maximum impairment and a score of 7 indicating no impairment.

Sample size calculation was based on a study by Dalcin et al.¹⁴14 Dalcin PT, Menegotto DM, Zanonato A, Franciscatto L, Soliman F, Figueiredo M, et al. Factors associated with uncontrolled asthma in Porto Alegre, Brazil. Braz J Med Biol Res. 2009;42(11):1097-103. https://doi.org/10.1590/S0100-879X2009005000035
https://doi.org/10.1590/S0100-879X200900... For a proportion of 60% of female patients with uncontrolled asthma, a proportion of 45% of male patients with uncontrolled asthma, a total width of 0.15, a type I error of 0.05 (two-sided), and a type II error of 0.20 (or a study power of 0.80), the required sample size was calculated to be 186.

Statistical analysis of the data was performed with the IBM SPSS Statistics software package, version 20.0 (IBM Corporation, Armonk, NY, USA). Quantitative data were expressed as mean ± standard deviation or median (interquartile range), and qualitative data were expressed as n (%). Categorical variables were compared by the chi-square test with adjusted standardized residuals, Yates’ correction or Fisher’s exact test being used as appropriate. For continuous variables, the Student’s t-test or the Mann-Whitney U test was used for between-group comparisons. All statistical tests were two-tailed, and the level of significance was set at p < 0.05.

RESULTS

Between March and December of 2013, we evaluated 344 patients with asthma. Of those, 75 declined to participate, 53 were excluded because they had chronic lung diseases other than asthma, 8 were excluded because they were smokers or former smokers (with a smoking history of more than 10 pack-years), and 10 were excluded because they failed to have all of the required assessments performed. Therefore, the final sample consisted of 198 patients.

The general characteristics of the participating patients are presented in Table 1. Of the 198 participants, 162 (81.8%) were female. The mean age was 56.2 ± 14.8 years. With regard to the severity of asthma, 144 patients (72.2%) had severe persistent asthma, 31 (15.7%) had moderate persistent asthma, and 23 (11.6%) had mild persistent asthma. With regard to the level of asthma control, 118 patients (59.6%) had uncontrolled asthma, 28 (14.1%) had partly controlled asthma, and 52 (26.3%) had well-controlled asthma. The mean BMI was 29.6 ± 5.7 kg/m², 83 patients (41.9%) being classified as obese, 72 (36.4%) being classified as overweight, and 43 (21.7%) being classified as normal weight.

Table 2 shows a comparison between the genders in terms of clinical characteristics, health-related quality of life, level of asthma control, lung function, and nutritional status. The prevalence of White patients was higher among males than among females (91.7% vs. 72.0%; p = 0.024). Quality of life was lower in females than in males in all four AQLQ domains: symptoms (3.8 ± 1.5 vs. 4.6 ± 1.7; p = 0.006); activity limitation (3.6 ± 1.3 vs. 4.4 ± 1.5; p = 0.001); emotional function (3.6 ± 1.9 vs. 4.5 ± 1.7; p = 0.014); and environmental stimuli (3.2 ± 1.6 vs. 4.3 ± 1.9; p = 0.001). The proportion of patients with uncontrolled asthma was higher among females than among males (63.0% vs. 44.4%; p = 0.041). In addition, the BMI and percentage of body fat were higher in females than in males (30.2 ± 5.8 kg/m² and 37.4 ± 6.4% vs. 26.9 ± 4.5 kg/m² and 26.5 ± 7.4%; p = 0.002 and p < 0.001, respectively). Chronic comorbidities were more commonly reported by females than by males (68.5% vs. 38.9%; p = 0.001), as were cardiovascular comorbidities (58.0% vs. 36.1%; p = 0.028). There were no significant differences between the genders regarding age (p = 0.805), asthma severity (p = 0.401), percent predicted FVC (p = 0.078), or percent predicted FEV₁ (p = 0.085). In addition, there was no association between menopause and the study outcomes.

DISCUSSION

In the present study, females predominated among adult patients with asthma treated at a referral outpatient clinic in southern Brazil. Health-related quality of life was found to be lower in females than in males in all four AQLQ domains. In addition, the proportion of patients with uncontrolled asthma was higher among females than among males, as were the BMI and percentage of body fat. Furthermore, comorbidities were more commonly reported by females than by males.

The high prevalence of asthma in adult females in the present study is consistent with the literature.²⁰20 Dijkstra A, Howard TD, Vonk JM, Ampleford EJ, Lange LA, Bleecker ER, Meyers DA, et al. Estrogen receptor 1 polymorphisms are associated with airway hyperresponsiveness and lung function decline, particularly in female subjects with asthma. J Allergy Clin Immunol. 2006;117(3):604-11. https://doi.org/10.1016/j.jaci.2005.11.023
https://doi.org/10.1016/j.jaci.2005.11.0...

21 Reddel HK, Taylor DR, Bateman ED, Boulet LP, Boushey HA, Busse WW, et al. An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med. 2009;180(1):59-99. https://doi.org/10.1164/rccm.200801-060ST
https://doi.org/10.1164/rccm.200801-060S... ^-2222 de Carvalho-Pinto RM, Cukier A, Angelini L, Antonangelo L, Mauad T, Dolhnikoff M, et al. Clinical characteristics and possible phenotypes of an adult severe asthma population. Respir Med. 2012;106(1):47-56. https://doi.org/10.1016/j.rmed.2011.08.013
https://doi.org/10.1016/j.rmed.2011.08.0... Zillmer et al.¹⁰10 Zillmer LR, Gazzotti MR, Nascimento OA, Montealegre F, Fish J, Jardim JR. Gender differences in the perception of asthma and respiratory symptoms in a population sample of asthma patients in four Brazilian cities. J Bras Pneumol. 2014;40(6):591-8. https://doi.org/10.1590/S1806-37132014000600002
https://doi.org/10.1590/S1806-3713201400... interviewed 400 asthma patients in four Brazilian cities and reported that 272 (68%) were female. Dursun et al.²³23 Dursun AB, Kurt OK, Bayiz H, Ozkan E, Cakaloglu A, Karasoy D. Does gender affect asthma control in adult asthmatics? Chron Respir Dis. 2014;11(2):83-7. https://doi.org/10.1177/1479972314527468
https://doi.org/10.1177/1479972314527468... studied 242 adult patients with asthma in Turkey and reported that 77.3% were female. Schatz & Camargo²⁴24 Schatz M, Camargo CA Jr. The relationship of sex to asthma prevalence, health care utilization, and medications in a large managed care organization. Ann Allergy Asthma Immunol. 2003;91(6):553-8. https://doi.org/10.1016/S1081-1206(10)61533-5
https://doi.org/10.1016/S1081-1206(10)61... used computerized data from Kaiser-Permanente Southern California in order to identify patients with asthma. Among the 60,694 asthma patients, the female-male prevalence ratio was approximately 65:35 in the 23- to 64-year age bracket. Previous studies conducted at our institution in different settings and involving different samples of adults have shown a high (68.6-75%) prevalence of females seeking hospital treatment for asthma.⁷7 Forte GC, Grutcki DM, Menegotto SM, Pereira RP, Dalcin Pde T. Prevalence of obesity in asthma and its relations with asthma severity and control. Rev Assoc Med Bras (1992). 2013;59(6):594-9. https://doi.org/10.1590/S0104-42302013000600014
https://doi.org/10.1590/S0104-4230201300... ^,2525 Dalcin Pde T, da Rocha PM, Franciscatto E, Kang SH, Menegotto DM, Polanczyk CA, et al. Effect of clinical pathways on the management of acute asthma in the emergency department: five years of evaluation. J Asthma. 2007;44(4):273-9. https://doi.org/10.1080/02770900701247020
https://doi.org/10.1080/0277090070124702... ^,2626 Piovesan DM, Menegotto DM, Kang S, Franciscatto E, Millan T, Hoffmann C, et al. Early prognosis of acute asthma in the emergency room. J Bras Pneumol. 2006;32(1):1-9. https://doi.org/10.1590/S1806-37132006000100004
https://doi.org/10.1590/S1806-3713200600... There is compelling evidence that sex hormones are major determinants of at least these biological differences in asthma prevalence.²⁰20 Dijkstra A, Howard TD, Vonk JM, Ampleford EJ, Lange LA, Bleecker ER, Meyers DA, et al. Estrogen receptor 1 polymorphisms are associated with airway hyperresponsiveness and lung function decline, particularly in female subjects with asthma. J Allergy Clin Immunol. 2006;117(3):604-11. https://doi.org/10.1016/j.jaci.2005.11.023
https://doi.org/10.1016/j.jaci.2005.11.0... It has been reported that estrogen receptor 1 polymorphisms are associated with bronchial hyperresponsiveness and lung function decline, especially in females with asthma.⁴4 Melgert BN, Ray A, Hylkema MN, Timens W, Postma DS. Are there reasons why adult asthma is more common in females? Curr Allergy Asthma Rep. 2007;7(2):143-50. https://doi.org/10.1007/s11882-007-0012-4
https://doi.org/10.1007/s11882-007-0012-...

The overall health-related quality of life in our sample was moderate, AQLQ scores being significantly lower among females than among males. Other studies have shown that health-related quality of life is worse in female asthma patients than in male asthma patients.¹¹11 Wijnhoven HA, Kriegsman DM, Snoek FJ, Hesselink AE, de Haan M. Gender differences in health-related quality of life among asthma patients. The J Asthma. 2003;40(2):189-99. https://doi.org/10.1081/JAS-120017990
https://doi.org/10.1081/JAS-120017990... ^,2727 Trawick DR, Holm C, Wirth J. Influence of gender on rates of hospitalization, hospital course, and hypercapnea in high-risk patients admitted for asthma: a 10-year retrospective study at Yale-New Haven Hospital. Chest. 2001;119(1):115-9. https://doi.org/10.1378/chest.119.1.115
https://doi.org/10.1378/chest.119.1.115... ^,2828 Jang Y, Yoo H. Gender differences of health behaviors and quality of life of Koreans with asthma. Open J Nurs. 2013;6(3):420-5. https://doi.org/10.4236/ojn.2013.36057
https://doi.org/10.4236/ojn.2013.36057... In a cross-sectional study, Lisspers et al.²⁹29 Lisspers K, Ställberg B, Janson C, Johansson G, Svärdsudd K. Sex-differences in quality of life and asthma control in Swedish asthma patients. J Asthma. 2013;50(10):1090-5. https://doi.org/10.3109/02770903.2013.834502
https://doi.org/10.3109/02770903.2013.83... investigated 1,226 patients in a primary care setting and 499 patients in a secondary care setting. They concluded that quality of life and the level of asthma control were lower in young females than in young males, although no such differences were found between older females and older males. Female sex hormones could be an important factor affecting these outcomes. Correia de Sousa et al.³⁰30 Correia de Sousa J, Pina A, Cruz AM, Quelhas A, Almada-Lobo F, Cabrita J, et al. Asthma control, quality of life, and the role of patient enablement: a cross-sectional observational study. Prim Care Respir J. 2013;22(2):181-7. https://doi.org/10.4104/pcrj.2013.00037
https://doi.org/10.4104/pcrj.2013.00037... found that females were 3.8 times more likely to have poorer quality of life than were males. This finding was associated with higher rates of anxiety and depression in the female population.¹³13 Belloch A, Perpi-á M, Martínez-Moragón E, de Diego A, Martínez-Francés M. Gender differences in health-related quality of life among patients with asthma. J Asthma. 2003;40(8):945-53. https://doi.org/10.1081/JAS-120024595
https://doi.org/10.1081/JAS-120024595... A possible explanation for this finding is that being overweight and having uncontrolled asthma is more common in females than in males. These findings are consistent with those of Xu et al.,³¹31 Xu KY, Wisnivesky JP, Martynenko M, Mhango G, Busse PJ, Wolf MS, et al. Assessing the association of obesity and asthma morbidity in older adults. Ann Allergy Asthma Immunol. 2016;117(1):33-7. https://doi.org/10.1016/j.anai.2016.04.027
https://doi.org/10.1016/j.anai.2016.04.0... who investigated the association between obesity and asthma outcomes in older adults.

In the present study, asthma severity was assessed by the GINA classification system on the basis of daily medication use,¹1 Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention 2016. Bethesda: GINA; 2016. meaning that although effective therapy was able to control the disease, it did not interfere with the classification of disease severity. The proportion of patients with severe persistent asthma was high in the present study (i.e., 72.7%). However, asthma severity and lung function (as assessed by percent predicted FVC and FEV₁) did not differ between males and females. In contrast, Carvalho-Pinto et al.²²22 de Carvalho-Pinto RM, Cukier A, Angelini L, Antonangelo L, Mauad T, Dolhnikoff M, et al. Clinical characteristics and possible phenotypes of an adult severe asthma population. Respir Med. 2012;106(1):47-56. https://doi.org/10.1016/j.rmed.2011.08.013
https://doi.org/10.1016/j.rmed.2011.08.0... reported that the female predominance in their group of patients suggested that severe asthma was a gender-related disease.

Asthma control, which is defined as the extent to which the various manifestations of asthma are reduced or removed by treatment, is increasingly receiving attention not only in clinical trials but also in clinical practice.²¹21 Reddel HK, Taylor DR, Bateman ED, Boulet LP, Boushey HA, Busse WW, et al. An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med. 2009;180(1):59-99. https://doi.org/10.1164/rccm.200801-060ST
https://doi.org/10.1164/rccm.200801-060S... In the present study, the proportion of patients with uncontrolled asthma was higher among females than among males. Previous studies have shown a lower level of asthma control in females than in males, despite a higher use of inhaled corticosteroids and more frequent visits to an asthma treatment center among the former.²²22 de Carvalho-Pinto RM, Cukier A, Angelini L, Antonangelo L, Mauad T, Dolhnikoff M, et al. Clinical characteristics and possible phenotypes of an adult severe asthma population. Respir Med. 2012;106(1):47-56. https://doi.org/10.1016/j.rmed.2011.08.013
https://doi.org/10.1016/j.rmed.2011.08.0... ^,3232 Temprano J, Mannino DM. The effect of sex on asthma control from the National Asthma Survey. J Allergy Clin Immunol. 2009;123(4):854-60. https://doi.org/10.1016/j.jaci.2008.12.009
https://doi.org/10.1016/j.jaci.2008.12.0... It has also been reported that females are 3.2 times more likely to have uncontrolled asthma than are males.³⁰30 Correia de Sousa J, Pina A, Cruz AM, Quelhas A, Almada-Lobo F, Cabrita J, et al. Asthma control, quality of life, and the role of patient enablement: a cross-sectional observational study. Prim Care Respir J. 2013;22(2):181-7. https://doi.org/10.4104/pcrj.2013.00037
https://doi.org/10.4104/pcrj.2013.00037... Poor asthma control in females might also be related to being overweight. Although mechanisms linking both conditions are still poorly understood, there is evidence that obesity impairs clinical control.³³33 Cardoso MDL, D'Oliveira RAJ, Salame FM. Obesity and Quality of Life in Asthmatic Adult Patients in the Amazon Region. Am J Respir Crit Care Med. 2017;195:A7458. Although clinical observations indicate that menopause is generally associated with weight gain, exacerbation of asthma, and, consequently, worsening of asthma control,³⁴34 Balzano G, Fuschillo S, Melillo G, Bonini S. Asthma and sex hormones. Allergy. 2001:56(1):13-20. https://doi.org/10.1034/j.1398-9995.2001.00128.x
https://doi.org/10.1034/j.1398-9995.2001... we found no association between menopause and the study outcomes.

Obesity is defined as an increase in body weight resulting from excess body fat. Previous studies have shown a high prevalence of obesity among asthma patients treated at an asthma outpatient clinic,⁷7 Forte GC, Grutcki DM, Menegotto SM, Pereira RP, Dalcin Pde T. Prevalence of obesity in asthma and its relations with asthma severity and control. Rev Assoc Med Bras (1992). 2013;59(6):594-9. https://doi.org/10.1590/S0104-42302013000600014
https://doi.org/10.1590/S0104-4230201300... ^,3535 Barros LL, Souza-Machado A, Corrêa LB, Santos JS, Cruz C, Leite M, et al. Obesity and poor asthma control in patients with severe asthma. J Asthma. 2011;48(2):171-6. https://doi.org/10.3109/02770903.2011.554940
https://doi.org/10.3109/02770903.2011.55... ^,3636 Pelegrino NR, Faganello MM, Sanchez FF, Padovani CR, Godoy Id. Relationship between body mass index and asthma severity in adults. J Bras Pneumol. 2007;33(6):641-6. https://doi.org/10.1590/S1806-37132007000600006
https://doi.org/10.1590/S1806-3713200700... a finding that is consistent with those of the present study, in which the BMI and percentage of body fat were found to be higher in females than in males. Of the patients in our sample, 155 (78.3%) were overweight (i.e., had a BMI ≥ 25 kg/m²), and 133 (82%) were female. A high BMI has been associated with poor asthma control and quality of life.²²22 de Carvalho-Pinto RM, Cukier A, Angelini L, Antonangelo L, Mauad T, Dolhnikoff M, et al. Clinical characteristics and possible phenotypes of an adult severe asthma population. Respir Med. 2012;106(1):47-56. https://doi.org/10.1016/j.rmed.2011.08.013
https://doi.org/10.1016/j.rmed.2011.08.0... ^,3333 Cardoso MDL, D'Oliveira RAJ, Salame FM. Obesity and Quality of Life in Asthmatic Adult Patients in the Amazon Region. Am J Respir Crit Care Med. 2017;195:A7458. Another finding that might have been influenced by excess weight and body fat is lung function. Dunn et al.³⁷37 Dunn RM, Lehman E, Chinchilli VM, Martin RJ, Boushey HA, Israel E, et al. Impact of Age and Gender on Response to Asthma Therapy. Am J Respir Crit Care Med. 2015;192(5):551-8. https://doi.org/10.1164/rccm.201503-0426OC
https://doi.org/10.1164/rccm.201503-0426... found that FEV₁ values were significantly higher in females than in males (84.5% vs. 81.1%; p < 0.001). However, in the present study, no significant differences were found between the genders regarding lung function parameters (i.e., percent predicted FVC, FEV₁, and FEV₁/FVC).

Asthma is often associated with various comorbidities, the most common being rhinitis, sinusitis, gastroesophageal reflux disease, obstructive sleep apnea, hormonal disorders, and psychopathologies.³⁸38 Boulet LP, Boulay MÈ. Asthma-related comorbidities. Expert Rev Respir Med. 2011;5(3):377-93. https://doi.org/10.1586/ers.11.34
https://doi.org/10.1586/ers.11.34... These conditions might share a common pathophysiological mechanism with asthma, influence asthma control, or be more prevalent in asthma patients, having, however, no obvious influence on asthma.³⁸38 Boulet LP, Boulay MÈ. Asthma-related comorbidities. Expert Rev Respir Med. 2011;5(3):377-93. https://doi.org/10.1586/ers.11.34
https://doi.org/10.1586/ers.11.34... Peters et al.³⁹39 Peters SP, Jones CA, Haselkorn T, Mink DR, Valacer DJ, Weiss ST. Real-world Evaluation of Asthma Control and Treatment (REACT): findings from a national Web-based survey. J Allergy Clin Immunol. 2007;119(6):1454-61. https://doi.org/10.1016/j.jaci.2007.03.022
https://doi.org/10.1016/j.jaci.2007.03.0... reported that comorbidities were significantly associated with uncontrolled asthma. In the present study, chronic and cardiovascular comorbidities were more commonly reported by females than by males. Cazzola et al.⁴⁰40 Cazzola M, Calzetta L, Bettoncelli G, Novelli L, Cricelli C, Rogliani P. Asthma and comorbid medical ill-ness. Eur Respir J. 2011;38(1):42-9. https://doi.org/10.1183/09031936.00140310
https://doi.org/10.1183/09031936.0014031... reported that being female slightly increased the association of all cardiovascular diseases with asthma. They also reported that the association of asthma with diabetes mellitus, dyslipidemia, osteoporosis, depression, and psychiatric disorders was stronger in females than in males.

The present study has potential limitations. Given that it was a cross-sectional study, it was impossible to establish a temporal sequence between gender and the factors studied. In addition, this was a single-center study, and the sample size was small. Furthermore, the study population was selected from among patients treated at a referral center and was probably biased toward those with disease that is more severe.

In summary, health-related quality of life is lower in adult females with asthma than in adult males with asthma, as evidenced by lower scores in all four AQLQ domains. In addition, the proportion of patients with uncontrolled asthma is higher among females than among males, as are the BMI, percentage of body fat, and reported rates of comorbidities.

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