|Year : 2022 | Volume
| Issue : 1 | Page : 28-33
Influence of thyroid status on pulmonary functions in bronchial asthma patients
Kaushal Kumar1, Aarti Sood Mahajan1, Dayaram Haldwani1, Dharam Pal Bhadoria2, Binita Goswami3
1 Department of Physiology, Maulana Azad Medical College and Associated Lok Nayak Hospital, New Delhi, India
2 Department of Pulmonary Medicine, Maulana Azad Medical College and Associated Lok Nayak Hospital, New Delhi, India
3 Department of Biochemistry, Maulana Azad Medical College and Associated Lok Nayak Hospital, New Delhi, India
|Date of Submission||26-Jul-2022|
|Date of Acceptance||16-Dec-2022|
|Date of Web Publication||16-Feb-2023|
Dr. Aarti Sood Mahajan
Director Professor, Department of Physiology, Maulana Azad Medical College & Lok Nayak Hospital, New Delhi- 110002
Source of Support: None, Conflict of Interest: None
BACKGROUND: Asthma is a serious global health problem affecting all age groups. It is being recognized for its health impact on the working status of adults, and uncontrolled asthma is associated with significant morbidity, mortality, and socioeconomic problems. The knowledge of comorbidities of asthma, including thyroid disorders, is important for its management.
METHODOLOGY: A case–control study was conducted in 60 diagnosed patients of bronchial asthma in the age group of 20–40 years attending medicine outpatient departments and Chest Clinic of Lok Nayak Hospital, New Delhi. Thirty controls were taken from the normal population. Pulmonary function tests using "Schiller SP1 portable top spirometer" were done, and forced vital capacity (FVC), forced expiratory volume in 1st s (FEV1), FEV1/FVC ratio, and peak expiratory flow rate (PEFR) were analyzed. The thyroid function was assessed by estimating levels of serum thyroid-stimulating hormone (TSH), free T3, and free T4 using the Cobas e411 autoanalyzer.
RESULTS: Based on TSH analysis of asthmatic patients, 25% were hypothyroid, 16.7% were hyperthyroid, and 58.3% were euthyroid. There were significant reductions in FEV1, FEV1/FVC ratio, and PEFR in asthmatics compared to controls, but no significant differences were found in these parameters among the asthmatics with different thyroid status.
CONCLUSION: The thyroid functions varied in asthmatics. However, the variation in the thyroid function did not affect the pulmonary function in asthmatic patients.
Keywords: Bronchial asthma, comorbidity, pulmonary function test, thyroid function
|How to cite this article:|
Kumar K, Mahajan AS, Haldwani D, Bhadoria DP, Goswami B. Influence of thyroid status on pulmonary functions in bronchial asthma patients. Indian J Allergy Asthma Immunol 2022;36:28-33
|How to cite this URL:|
Kumar K, Mahajan AS, Haldwani D, Bhadoria DP, Goswami B. Influence of thyroid status on pulmonary functions in bronchial asthma patients. Indian J Allergy Asthma Immunol [serial online] 2022 [cited 2023 Apr 2];36:28-33. Available from: https://www.ijaai.in/text.asp?2022/36/1/28/369804
| Introduction|| |
Bronchial asthma has been found to be associated with various comorbidities such as chronic obstructive pulmonary disease, gastroesophageal reflux disease, hyperthyroidism, and hypothyroidism. The incidence of hyperthyroidism has been found to be significantly more in asthmatics compared to nonasthmatics,, and it is shown to be positively associated with increasing severity of bronchial asthma. In addition, when concomitant hyperthyroidism was treated, asthmatic patients improved, and a decreased bronchoconstrictor response to inhaled histamine was observed., In addition, the development of hypothyroidism may ameliorate coexistent asthma, and the treatment of a hypothyroid state can result in worsening of airway obstruction and should be done cautiously to prevent the relapse of thyrotoxicosis and exacerbation of asthma. The plasma antithyroid peroxidase antibody (anti-TPO antibodies) levels were found to be significantly higher in the group with asthma compared to control. It has also been suggested that asthma may lead to increase in cytokines which inhibit the activity of thyroid-stimulating hormone (TSH) and suppress the conversion of T4 to T3, thereby decreasing its level.
It is necessary to understand the role of comorbidities in asthma as they can affect pulmonary functions, the severity of disease, and duration of treatment. Awareness of the interactions between thyroid disease and asthma in patients and understanding the biochemical basis of the mechanisms involved are necessary for the proper management of both disorders. Therefore, this study aimed to find out the association of comorbidity of an altered thyroid status and pulmonary functions in asthma patients.
| Methodology|| |
A cross-sectional analytical study was carried out between October 2018 and March 2020 in diagnosed patients of bronchial asthma attending medicine OPDs and Chest Clinic of Lok Nayak Hospital, associated with Maulana Azad Medical College (MAMC), New Delhi, fulfilling the specified inclusion and exclusion criteria and controls, from staff, relatives of patients, and the general population.
All participants of either gender were over 18 years and <40 years of age. Bronchial asthma in patients was confirmed by the physician/investigations. Participants with a body mass index (BMI) of ≥25 kg/m2, known cases of thyroid disorders on treatment, smokers (both past and present), asthmatic patients in severe acute exacerbations, those with occupational lung diseases, conditions likely to affect the performance of the study participants during pulmonary function testing such as neuromuscular disease and skeletal disorders, patients who have moderate-to-severe dyspnea, hepatic, renal, and cardiovascular diseases, diabetes mellitus, cancer, systemic inflammatory disorders, known allergic disorders, and tuberculosis were excluded from the study. All patients were being treated for asthma. The controls were age-matched healthy individuals with no history of asthma or thyroid disease.
Asthma patients were assigned into cases (Group 1) and were further classified on the basis of TSH values into: Group 1A: TSH (<0.5 mIU/L), Group 1B: TSH (0.5–4.7 mIU/L), and Group 1C: TSH (>4.7 mIU/L). Ethical clearance was obtained from the Institutional Ethical Committee for Human Research. The patient information sheet and consent form were available in both English and Hindi (the local language). For those who did not understand, it was explained, and an informed written consent was taken from each participant after enrolment.
The patients were interviewed to collect demographic information. A detailed history was taken and a clinical examination including anthropometry (height and weight) was done for each participant. The parameters recorded were age in years; height was recorded in centimeter measured using an anthropometric scale with a sensitivity of 0.5 cm. Weight was recorded using the same anthropometric scale with a capacity of 300 LBS (pounds). The sensitivity of scale was 0.25 LBS. Weight recorded in pound was converted into kg (1 LBS = 0.453 kg). The BMI was computed as body weight in kilograms divided by the square of standing height in meters (kg/m2).
Pulmonary function test (PFT) parameters analyzed for the study were forced vital capacity (FVC), forced expiratory volume in the 1st s (FEV1), FEV1/FVC ratio, and peak expiratory flow rate (PEFR). The instrument used was a calibrated and validated SP1 portable spirometer by Schiller Healthcare India Pvt. Ltd, Delhi; PFT volumes were represented in liters, flow rates in liters per second, and the percentage of predicted values on the basis of age, height, weight, ethnicity, and sex according to the ERS 1993 by Zapletal for the Indian population. The spirometry procedure adopted was as per the American Thoracic Society guidelines. The participants were called in the morning hours (9:00 a.m.–10:00 a.m.) in the Respiratory Laboratory of the Pulmonary Medicine Division of the Department of Medicine in the hospital.
The procedure of test was explained to each participant, and the method of testing on the spirometer was demonstrated. All the tests were performed in a quiet and isolated room, and the temperature was maintained around 23°C–25°C. The participants were allowed to adapt to the experimental conditions, and ample time was given to relax. Every effort was made to allay apprehension and promote cooperation of the participants. The test was performed with the participant in a sitting position, wearing comfortable clothing and advised to use a nose clip to occlude the nose. The mouthpiece of the instrument was put inside the mouth with the lips closed properly around it to prevent any leak during the procedure. Initially, the participant was allowed to take a few normal breaths to get accustomed to the equipment and then asked to take in a deep inspiration and immediately blow out with the maximum force, continue to exhale while maintaining the force till possible, and then complete the maneuver with a deep inspiration. FEV1 and FVC were calculated from the flow volume curve. The highest value of the three measurements was used, and FEV1/FVC (%) was computed. The PFT reversibility was tested after the inhalation of 200–400 μg salbutamol and taking rest for 20 min. Diagnosis and severity of bronchial asthma were made on the Global Initiative for Asthma guidelines, 2018. All values were recorded, and the reports were obtained in a printed format.
Thyroid function test
A blood sample of 2 ml of 8 h fasting venous sample was taken in the plain vial from each participant. TSH, free thyroxine (fT4), free triiodothyronine (fT3), and anti-TPO antibodies were measured in the Department of Biochemistry MAMC, New Delhi, using the Cobas e 411 autoanalyzer, Switzerland, 2014.
All statistical analyses were performed using SPSS-25 statistical software (Manufacturer: International Business Machines Corporation (IBM)). Continuous variables were normally distributed and were presented as mean ± standard deviation. The unpaired Student's t-test was used to compare the BMI between cases and controls. For comparing the PFT and thyroid function test (TFT) parameters between cases and controls, the unpaired t-test for parametric distribution and the Mann–Whitney test for nonparametric distribution were used. Thyroid status between both groups at different intervals was compared using the Chi-square test. For comparing PFT parameters between cases with or without normal thyroid function and controls, ANOVA was used.
| Results|| |
The mean and standard deviation of the age of patients was 31.95 ± 6.34 and that of controls was 31.73 ± 6.35 (P = 0.87). The BMI was 22.57 ± 1.66 and 22.70 ± 1.38, P = 0.71, respectively. The PFT are shown in [Table 1], showing the decreased values in asthma patients and a significant difference between the patients and controls. [Table 2] shows the comparison of TFT between both groups. All the parameters were within normal limits in both groups; however, the value of fT3 and TSH levels was different between the cases and controls, suggesting that asthma cases have an altered thyroid function with higher thyroid levels [Figure 1]. A detailed analysis of thyroid status was done in cases and controls, as shown in [Table 3]. The results show that irrespective of the mean values as a group, in both the control and cases, there were a percentage of participants who had high or low TSH, T4, and T3 values.
|Figure 1: The thyroid functions (TSH, T3, and T4) in asthmatic patients and controls. TSH: Thyroid-stimulating hormone|
Click here to view
|Table 1: The comparison of pulmonary function test between asthma patients and the control group|
Click here to view
|Table 2: The comparison of thyroid function test between asthma patients and the control group|
Click here to view
|Table 3: The comparison of a detailed analysis of thyroid status between both asthma patients and control group|
Click here to view
On analysis of asthmatic subgroups, based on TSH value as shown in [Table 4] and [Table 5], a significant decrease in FEV1, PEFR, and FEV1/FVC ratio (P < 0.001) in all three groups compared to controls was seen. However, within asthmatics, there was no statistical difference in PFT depending on the thyroid status. Therefore, the altered thyroid status did not affect pulmonary function in our study. The Spearman correlation analysis [Table 6] showed a significant negative relationship of fT3 with FEV1 (high-TSH group) and PEFR (both high- and low-TSH group) and between FT4 and FEV1/FVC ratio (high-TSH group).
|Table 4: The comparison of pulmonary function parameters between asthma patients (cases) with or without normal thyroid function and controls|
Click here to view
|Table 5: ANOVA post hoc P value analysis for the comparison of pulmonary function parameters between asthma patients (cases) with or without normal thyroid function and controls|
Click here to view
|Table 6: Correlation between thyroid function parameters pulmonary function tests (forced vital capacity, forced expiratory volume in 1st s, forced expiratory volume/forced vital capacity ratio, and peak expiratory flow rate) among low and high thyroid-stimulating hormone value in asthma patients|
Click here to view
| Discussion|| |
The aim of this observational cross-sectional study was to assess and compare the pulmonary function test and thyroid status in asthmatics and nonasthmatics controls, to look for comorbidity of asthma and thyroid dysfunction and its effect on pulmonary function. It is known that the comorbidities associated with asthma may influence its expression and severity, share a pathophysiological mechanism, affect diagnosis or assessment, and effect efficacy or adherence to therapy. There was no difference in the two groups of adults on the basis of age and BMI, and although obesity has been recognized as comorbidity in asthma, the patients included in our study were not obese.
In a study comparing asthmatics and controls, the association of anti-TPO antibody and asthma has been reported, although the authors did not find the thyroid hormone status to be different. Our study varied as the TFT showed higher fT3 and decreased TSH values in asthmatics, although overall, the values were within the normal range in both groups. The values of fT4 and anti-TPO were similar in cases and controls in our study. These variations in thyroid functions in patients were perhaps diagnosed for the first time, and repeated measurements are required over a time to confirm this.
There have been previous studies that have found deranged thyroid status in asthmatic patients. It has been documented that asthma may coexist with hyperthyroidism, and correlation between asthma and hyperthyroidism was seen in a study done in Saudi Arabia. Moreover, the improvement of asthma and increased bronchial reactivity occur following the treatment of thyrotoxicosis.,
A decreased fT3 is known to be associated with acute exacerbation of asthma compared to stabilized patients. The mechanisms such as hypoxia, metabolic changes in the thalamus-pituitary complex, infection, and the influence of cytokines can influence the levels of TSH, T3, and T4. Hypoxia may trigger mechanisms for saving oxygen, which downregulates the step-up deiodinase activity, and the retention of carbon dioxide markedly reduces the thyroid hormone levels. However contradictory reports have also suggested a normal thyroid function (TSH and T4) in asthmatics.
In the current study, the thyroid values, suggestive of both hyper- and hypothyroidism, were found on a detailed and individual analysis, as a comorbidity in asthma patients. There was a significant difference in their PFT contributed due to their thyroid status in patients and controls, but no difference was seen within asthmatics on the basis of TSH. In an Indian study, the relationship between factors such as severity, control of asthma, change in pulmonary functions in euthyroid, and hyper- and hypothyroid patients was compared. The authors suggested that all uncontrolled asthma patients should be investigated for thyroid disorders as it can affect its severity, and that an integrated approach should be used in the management of asthma. In a recent study, it has been documented that asthmatics above 30 years of age and within 3 years of being diagnosed had an increased risk of developing hyperthyroidism. Therefore, it is recommended that asthmatics should be screened for and carefully treated for thyroid dysfunction, especially in lieu of exacerbation of asthma with thyrotoxicosis. In addition, it has been suggested that reactive oxygen species may contribute to this exacerbation. Hypoxemia is important in determining the peripheral metabolism of the thyroid hormones, and PaO2 affects the total T3 and T4 ratio.
| Conclusion|| |
Therefore, in conclusion, an individual analysis of thyroid status in asthmatic patients depicted both increased and decreased thyroid function in asthmatics. Thus, thyroid dysfunction was present as a comorbidity in asthmatics, who did not have any prior history suggesting it. Deranged pulmonary function in asthmatics was seen irrespective of the variation in thyroid status.
The author would like to thank laboratory staff for their cooperation.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Panek M, Mokros Ł, Pietras T, Kuna P. The epidemiology of asthma and its comorbidities in Poland – Health problems of patients with severe asthma as evidenced in the province of Lodz. Respir Med 2016;112:31-8.
Goldacre M, Kurina L, Yeates D, Seagroatt V, Gill L. Use of large medical databases to study associations between diseases. QJM 2000;93:669-75.
Cockcroft DW, Silverberg JD, Dosman JA. Decrease in non-specific bronchial reactivity in an asthmatic following treatment of hyperthyroidism. Ann Allergy 1978;41:160-3.
Lipworth BJ, Dhillon DP, Clark RA, Newton RW. Problems with asthma following treatment of thyrotoxicosis. Br J Dis Chest 1988;82:310-4.
Rowe MS, MacKechnie HL. Hypothyroidism with coexistent asthma: Problems in management. South Med J 1984;77:401-2.
Samareh Fekri M, Shokoohi M, Gozashti MH, Esmailian S, Jamshidian N, Shadkam-Farokhi M, et al.
Association between anti-thyroid peroxidase antibody and asthma in women. Iran J Allergy Asthma Immunol 2012;11:241-5.
El Shabrawy RM, Atta AH, Rashad NM. Serum Anti-TPO and TPO Gene Polymorphism as a predictive factor for hidden autoimmune thyroiditis in patient with bronchial asthma and allergic rhinitis. Egypt J Immunol 2016;23:77-86.
Cazzola M, Calzetta L, Bettoncelli G, Novelli L, Cricelli C, Rogliani P. Asthma and comorbid medical illness. Eur Respir J 2011;38:42-9.
Graham BL, Steenbruggen I, Miller MR, Barjaktarevic IZ, Cooper BG, Hall GL, et al.
Standardization of spirometry 2019 update. An official American thoracic society and European respiratory society technical statement. Am J Respir Crit Care Med 2019;200:e70-88.
Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention; 2018. Available from: www.ginasthma.org. [Last accessed on 2022 Jan 18].
Syme NR, Toft AD, Stoddart M, Beckett GJ. Clinical performance of the Roche cobas e411 automated assay system for thyrotropin-receptor antibodies for the diagnosis of Graves' disease. Ann Clin Biochem 2011;48:471-3.
Boulet LP, Boulay MÈ. Asthma-related comorbidities. Expert Rev Respir Med 2011;5:377-93.
Tashiro H, Shore SA. Obesity and severe asthma. Allergol Int 2019;68:135-42.
Qashqary M, Tobaiqy M, Al-Sutari MM, Mujallad A, Alsheikh I. Prevalence of suspected cases of hyperthyroidism in Jeddah by using Wayne's scoring index. Cureus 2020;12:e11538.
Bingyan Z, Dong W. Impact of thyroid hormones on asthma in older adults. J Int Med Res 2019;47:4114-25.
Mohammad HA, Abdelfattah MT, Ali LH, Morsi ZI. Association between anti-thyroid peroxidase and anti-cytokeratin 18 autoantibodies and bronchial asthma in women. Egypt J Chest Dis Tuberc 2016; 65:7-14.
Rajguru NV, Jindal S, Kapadia V, Tripathi S, Prajapati D, Parikh A. A study of relationship between bronchial Asthma and thyroid disorders. Intern J Sci Res 2020;9:PRINT ISSN No. 2277-8179. [DOI.10.36106/ijsr].
Gau SY, Huang JY, Yong SB, Cheng-Chung Wei J. Higher risk of hyperthyroidism in people with asthma: Evidence from a nationwide, population-based cohort study. J Allergy Clin Immunol Pract 2022;10:751-8.e1.
Luong KV, Nguyen LT. Hyperthyroidism and asthma. J Asthma 2000;37:125-30.
Dimopoulou I, Ilias I, Mastorakos G, Mantzos E, Roussos C, Koutras DA. Effects of severity of chronic obstructive pulmonary disease on thyroid function. Metabolism 2001;50:1397-401.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]