Abstract
Background:
This study aims to evaluate the relationship of pulmonary symptoms and co-morbidity diseases with lung function in adult smokers.
Methods:
Three hundred and fifty men adults over the age of 20 were involved. Spirometry tests were performed for measuring FVC, FEV1, and FEV1% FVC. COPD was categorized into four stages (I–IV) by the (GOLD) criteria of post-bronchodilator FEV1/FVC <0.70. For comparing the mean of pulmonary functions regarding the following variables, pulmonary symptoms, and co-morbidity diseases, t-test was used. Spearman’s correlation analysis was performed to get association between stages of COPD and study variables. Further analysis using multiple regressions was conducted to confirm the predictors of the pulmonary functions. The level of significance is taken as P < 0.05.
Results:
The mean age of participants was 54.7543 ± 13.44. A total of 43 (19.5%) participants were COPD; 7% of them were Stage I, 23.3% were Stage II, 39.5% were Stage III, and 30.2% were Stage IV. The mean of FEV1 in participants with shortness of breath (P < 0.001), cough (P = 0.001), wheezing (P = 0.023), as well as cardiovascular disease (P = 0.038) was significantly less in compared to those without these symptoms and disease. Also the mean of FVC in participants with shortness of breath (P < 0.001) and cough (P = 0.029) was significantly less in compared to others. Finally, the mean of FEV1/FVC in participants with shortness of breath (P < 0.001), cough (P = 0.001), and wheezing (P = 0.01) was less. The relationship between stages of COPD and other variables indicated a significant association between stages of COPD and diabetes mellitus (β = -.342P = 0.030). According to linear regression model, shortness of breath was the only influential variable on FEV1 (B = -.383CI: -23.729, -12.155 P < 0.001), FVC (B = -.296CI: -.365CI: -15.336, -6.082 P < 0.001), and FEV1/FVC (B = -.365, CI: -18.362, -9.029 P < 0.001).
Conclusions:
Pulmonary symptoms including shortness of breath, cough, and wheezing influenced the lung function in adult smokers. Additionally, shortness of breath was associated with FEV1, FVC, and FEV1/FVC. Cardiovascular disease decreased FEV1 in smokers, whereas diabetes mellitus was associated with milder COPD stages.
Keywords: Co-morbidity, respiratory function tests, smoking cessation, symptoms
Introduction
Obstructive airway disease usually occurs with respiratory symptoms such as wheezing, shortness of breath, cough, and sputum.[1,2] Moreover, several co-morbid conditions such as cardiovascular disease and diabetes mellitus in association with COPD increased the rate of mortality.[3,4] Studies have shown that decreased lung function is a marker of premature mortality, especially in cardiovascular disease.[5,6] Respiratory symptoms[7,8] and decreased lung function[7,8] are both[9,10] individually related to higher mortality rates. Poor control of symptoms is one of the most common reasons why adults with obstructive airway disease go to the emergency room and see a doctor.[11] In addition, the decline in lung function, expressed in forced expiratory volume in one second (FEV1), is accelerated in adults with asthma than in adults without asthma.[12] The association between respiratory symptoms and impaired lung function has already been investigated in individuals with asthma, and cough is especially important.[13,14] However, the relationship between respiratory symptoms and lung function in adult smokers is unclear. Therefore, our aim was to clarify the relationship between pulmonary symptoms as well as underlying diseases with lung function.
Methods
Design and population
This cross-sectional study was conducted from November 2019 to April 2020 at AL-Zahra Hospital, Isfahan Medical University. This study was approved and funded by Isfahan Medical University in Code of Ethics (IR.MUI.MED.REC.1398.710). The inclusion criteria for the patients were being at the age of over 18 years having smoking, and in this study, the women did not meet the eligible criteria.
Each participant signed a consent form to take part in the study. The exclusion criteria for this study are: (a) presence of acute respiratory infections, (b) lung disease counting lung cancer, interstitial lung disease, tuberculosis, neuromuscular disorders, and pneumothorax, and (c) failing to perform technically acceptable respiratory function tests.
A total of 350 patients had inclusion criteria during the study period, but 129 participants were excluded according to the exclusion criteria for this study. Therefore, there were 221 participants evaluated in this study. An adult who has smoked 100 cigarettes in his or her lifetime and who currently smokes cigarettes defined “current smoker.”[15] All participants, with or without symptoms, asked to fill out a checklist requesting information on age, smoking habit including age of the onset smoking, duration of smoking (year), number of cigarette packs consumed daily; pulmonary symptoms including shortness of breath, cough, sputum, and wheezing; underlying disorders including diabetes mellitus,[16] hypertension,[17] cardiovascular diseases (myocardial infarction, stroke, heart failure, angina or transient ischemic attacks),[18,19,20] and gastric reflux disease[21] And then they were tested for their lung function.
Pulmonary function assessment
Spirometry was performed before and 15 minutes after the administration of 400 micrograms of salbutamol by trained technicians according to the standards of the American Thoracic Society (ATS) and the European Respiratory Society (ERS).[22] While seated, the participants were asked to make a forced exhalation followed by a forced inhalation. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and FEV1 percent in relation to the maximal FVC (FEV1%FVC) were recorded. FVC was characterized as the biggest acceptable curve of either forced expiratory or forced inspiratory vital capacity. Reported FEV1 is considered a good biological marker for the risk of obstructive pulmonary disease. If the quality of the spirometry was not satisfactory, the procedure was repeated until the best quality was achieved. The highest FVC and highest FEV1 values were selected from measurements that met the reproducibility criteria. A pulmonologist reviewed the quality of all the tests. Bronchodilator responsiveness (BDR) was calculated more than 12% changes of the baseline forced expiratory volume in one second (FEV1) if this also exceeds 200 mL according to ATS guidelines.[23] COPD was identified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria of post-bronchodilator FEV1/FVC <0.70. FEV1/FVC <70%, in combination with FEV1 ≥80% (Stage I), or 50%≤FEV1 <80% (Stage II), or 30% ≤ FEV1 < 50% (Stage III), or FEV1 ≤30% (Stage IV). ATS guidelines were used to assess bronchodilator response (BDR) (post FEV1 12% more than pre FEV1).[24]
Variable definition
Age was self-reported. Detailed assessments of smoking history were recorded as reported by the participants at the time of enrollment including age at which participants started smoking (year), duration of smoking (calculated as the difference between the age at time of quitting or time of enrollment and the age at smoking initiation), and the average number of cigarette packs consumed daily.[25] Pulmonary symptoms include shortness of breath which assessed by asking the question, “Do you have to walk slower than people of your age on the level because of breathlessness?”; and “Are you too breathless to leave the house or breathless on dressing or undressing?”, cough which assessed by asking the question, “Do you usually have a cough?”, sputum production assessed by question the patients “Do you usually bring up phlegm from your chest?”, wheezing assessed by asking the question “Does your chest ever sound wheezy or whistling apart from colds?”,[26] and gastric reflux disease assessed by asking “Do you have heartburn and an unpleasant taste in the back of the mouth?”.[21]
Subjects were classified as having diabetes if they reported either a diagnosis of diabetes at baseline or had impaired fasting or post-glucose load glucose levels (.140 mg/dL) upon examination. Subjects reporting a diagnosis of a previous myocardial infarction, stroke, heart failure, angina or transient ischemic attacks were classified as having cardiovascular disease at the baseline examination. Subjects were classified as having hypertension if they reported physician diagnosis of hypertension, were receiving treatment for hypertension, or had evidence of hypertension upon examination (diastolic blood pressure o90 mmHg or a systolic blood pressure o140 mmHg, based on three measurements).[27]
Study outcomes include pre/post FVC, pre/post FEV1, and pre/post FEV1/FVC measured by spirometry. COPD was defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria of post-bronchodilator FEV1/FVC <0.70 (22). Bronchodilator response (BDR) was calculated with (post FEV1 – preFEV1/preFEV1 ×100 is more than 12%).[24]
Statistical analysis
Data are presented as mean (SD) or frequency (percent). For comparing the mean of pulmonary functions in categories of variables, independent t-test was used. Pearson’s Chi-square test was done to get association between severity of COPD and the variables of study. Further analysis using multiple regressions was conducted to confirm the predictors of the pulmonary functions. The level of significance is taken as P < 0.05. Statistical analysis was conducted by the SPSS software version 16 (SPSS Inc., Chicago).
Results
Two hundred and twenty-one men participated in the study. The information about the measured variables is seen as frequency (percentage) or mean (SD) in Table 1. According to table, the mean age of participants was 54.75 ± 13.44. A total of 43 (19.5%) of them were COPD; 7% of them were Stage I, 23.3% were Stage II, 39.5% were Stage III, and 30.2% were Stage IV. For evaluation of bronchodilator response (BDR), we used ATS guidelines (post FEV1 – preFEV1/pre FEV1 × 100 more than 12%) and in 59 (26.7%) of participation, this criterion was positive.
Table 1.
Demographic and baseline information (n=221)
| Variables | Categories | Count (%)/Mean (SD) |
|---|---|---|
| Age | - | 54.75±13.44 |
| Age of the onset smoking (year) | - | 20.97±7.06 |
| Duration of smoking (year) | - | 30.84±14.22 |
| Number of cigarette packs consumed daily | - | 1.44±3.90 |
| Shortness of breath | No | 106 (48) |
| Yes | 115 (52) | |
| Cough | No | 131 (59.3) |
| Yes | 90 (40.7) | |
| Phlegm | No | 82 (37.1) |
| Yes | 139 (62.9) | |
| Wheezing | No | 92 (41.6) |
| Yes | 129 (58.4) | |
| Diabetes mellitus | No | 201 (91) |
| Yes | 20 (9) | |
| High blood pressure | No | 183 (82.8) |
| Yes | 38 (17.2) | |
| Cardiovascular disease | No | 186 (84.2) |
| Yes | 35 (15.8) | |
| Stomach reflex | No | 149 (67.4) |
| Yes | 72 (32.6) | |
| COPD* | No | 176 (80.4) |
| Yes | 43 (19.5) | |
| Severity (GOLD) | Stage I | 3 (7) |
| Stage II | 10 (23.3) | |
| Stage III | 17 (39.5) | |
| Stage IV | 13 (30.2) | |
| Bronchodilator response (BDR) | No | 162 (73.3) |
| Yes | 59 (26.7) | |
| Pre FEV1 (%)§ | - | 70.55±24.41 |
| Pre FVC (%)|| | - | 76.98±19.90 |
| Pre FEV1/FVC (%)¶ | - | 88.73±17.77 |
| Post FEV1 (%)** | - | 75.36±23.44 |
| Post FVC (%)†† | - | 80.73±18.12 |
| Post FEV1/FVC (%)‡‡ | - | 91.23±18.76 |
*Chronic Obstructive Lung Disease, §pre-bronchodilator forced expiratory volume in 1s, ||pre-bronchodilator forced vital capacity, ¶pre-bronchodilator forced expiratory volume in 1s percent in relation to the maximal forced vital capacity, **post-bronchodilator forced expiratory volume in 1s, ††post-bronchodilator forced vital capacity, ‡‡post-bronchodilator forced expiratory volume in 1s percent in relation to the maximal forced vital capacity
The mean of FEV1, FVC, and FEV1/FVC after use of bronchodilator with respect to different categorizations has been shown in Table 2. According to independent t-test, the mean of FEV1 in participants with shortness of breath (P < 0.001), cough (P = 0.001), wheezing (P = 0.023), as well as cardiovascular disease (P = 0.038) was significantly less in compared to those without the symptoms and diseases. Also the mean of FVC in participants with shortness of breath (P < 0.001) and cough (P = 0.029) was significantly less in comparison to others. Finally, the mean of FEV1/FVC in participants with shortness of breath (P < 0.001), cough (P = 0.001), and wheezing (P = 0.01) was less.
Table 2.
Independent samples t-test results of dependent and independent variables of the study
| Variables | n | Mean | SD | P | ||
|---|---|---|---|---|---|---|
| postFEV1** | Shortness of breath | No | 105 | 84.7048 | 17.63897 | P<0.001 |
| Yes | 114 | 66.7632 | 24.86968 | |||
| PostFVC†† | Shortness of breath | No | 105 | 86.3143 | 14.03657 | P<0.001 |
| Yes | 114 | 75.6053 | 19.92758 | |||
| postFEV1FVC‡‡ | Shortness of breath | No | 105 | 98.3619 | 14.83118 | P<0.001 |
| Yes | 114 | 84.6667 | 19.64628 | |||
| postFEV1** | Cough | No | 130 | 79.8769 | 22.69071 | 0.001 |
| Yes | 89 | 68.7753 | 23.08913 | |||
| postFVC†† | Cough | No | 130 | 82.9462 | 17.02224 | 0.029 |
| Yes | 89 | 77.5169 | 19.27558 | |||
| postFEV1FVC‡‡ | Cough | No | 130 | 94.7231 | 17.30753 | 0.001 |
| Yes | 89 | 86.1348 | 19.71513 | |||
| postFEV1** | Phlegm | No | 80 | 77.3000 | 22.69467 | 0.335 |
| Yes | 139 | 74.2518 | 23.87804 | |||
| postFVC†† | Phlegm | No | 80 | 81.2625 | 16.61762 | 0.74 |
| Yes | 139 | 80.4388 | 18.99318 | |||
| postFEV1FVC‡‡ | Phlegm | No | 80 | 93.5375 | 18.39231 | 0.16 |
| Yes | 139 | 89.9065 | 18.91050 | |||
| postFEV1** | Wheezing | No | 91 | 79.6154 | 22.36255 | 0.023 |
| Yes | 128 | 72.3438 | 23.81406 | |||
| postFVC†† | Wheezing | No | 91 | 82.2967 | 16.28530 | 0.28 |
| Yes | 128 | 79.6328 | 19.31621 | |||
| postFEV1FVC‡‡ | Wheezing | No | 91 | 95.0989 | 18.16165 | 0.01 |
| Yes | 128 | 88.4844 | 18.76711 | |||
| postFEV1** | Diabetes Mellitus | No | 199 | 75.4322 | 23.74005 | 0.89 |
| Yes | 20 | 74.7000 | 20.82787 | |||
| postFVC†† | Diabetes mellitus | No | 199 | 80.6834 | 18.21658 | 0.88 |
| Yes | 20 | 81.3000 | 17.65190 | |||
| postFEV1FVC‡‡ | Diabetes mellitus | No | 199 | 91.6683 | 18.86048 | 0.280 |
| Yes | 20 | 86.9000 | 17.61847 | |||
| postFEV1** | High blood pressure | No | 181 | 75.7845 | 23.71645 | 0.565 |
| Yes | 38 | 73.3684 | 22.30916 | |||
| postFVC†† | High blood pressure | No | 181 | 81.0221 | 17.73037 | 0.616 |
| Yes | 38 | 79.3947 | 20.10989 | |||
| postFEV1FVC‡‡ | High blood pressure | No | 181 | 91.6298 | 18.63930 | 0.496 |
| Yes | 38 | 89.3421 | 19.48149 | |||
| postFEV1** | Cardiovascular disease | No | 184 | 76.7935 | 22.96638 | 0.038 |
| Yes | 35 | 67.8571 | 24.83492 | |||
| postFVC†† | Cardiovascular disease | No | 184 | 81.6087 | 17.45906 | 0.104 |
| Yes | 35 | 76.1714 | 20.99087 | |||
| postFEV1FVC‡‡ | Cardiovascular disease | No | 184 | 91.9348 | 18.38198 | 0.205 |
| Yes | 35 | 87.5429 | 20.53740 | |||
| postFEV1** | Stomach reflux | No | 148 | 75.6149 | 23.36971 | 0.821 |
| Yes | 71 | 74.8451 | 23.76411 | |||
| postFVC†† | Stomach reflux | No | 148 | 81.7905 | 17.98875 | 0.216 |
| Yes | 71 | 78.5493 | 18.34572 | |||
| postFEV1FVC‡‡ | Stomach reflux | No | 148 | 90.6351 | 19.44402 | 0.497 |
| Yes | 71 | 92.4789 | 17.32204 | |||
| Yes | 148 | 75.6149 | 23.36971 | |||
A**Post-bronchodilator forced expiratory volume in 1s, ††post-bronchodilator forced vital capacity, ‡‡post-bronchodilator forced expiratory volume in 1s percent in relation to the maximal forced vital capacity
The relationship between stages of COPD and other variables was shown in Table 3. According to this table, there was a significant association between stages of COPD and diabetes mellitus (x2 = 8.59, P = 0.035).
Table 3.
Univariate associations between pulmonary symptoms, underling diseases, and stages of COPD. Pearson’s Chi-square test was used
| Stage I | Stage II | Stage III | Stage IV | Pearson Chi-square | P | |
|---|---|---|---|---|---|---|
| Shortness of breath | ||||||
| No | 1 (2.3) | 2 (4.7) | 4 (9.3) | 1 (2.3) | 1.74 | 0.629 |
| Yes | 2 (4.7) | 8 (18.6) | 13 (30.2) | 12 (27.9) | ||
| Cough | ||||||
| No | 0 (0) | 5 (11.6) | 8 (18.6) | 6 (14.0) | 2.59 | 0.459 |
| Yes | 3 (7) | 5 (11.6) | 9 (20.9) | 7 (16.3) | ||
| Phlegm | ||||||
| No | 0 (0) | 3 (7) | 7 (16.3) | 4 (9.3) | 2.07 | 0.558 |
| Yes | 3 (7) | 7 (16.3) | 10 (23.3) | 9 (20.9) | ||
| Wheezing | ||||||
| No | 0 (0) | 3 (7) | 6 (14) | 3 (7) | 1.79 | 0.616 |
| Yes | 3 (7) | 7 (16.3) | 11 (25.6) | 10 (23.3) | ||
| Diabetes mellitus | ||||||
| No | 1 (2.3) | 8 (18.6) | 16 (37.2) | 12 (27.9) | 8.59 | 0.035 |
| Yes | 2 (4.7) | 2 (4.7) | 1 (2.3) | 1 (2.3) | ||
| High blood pressure | ||||||
| No | 2 (4.7) | 9 (20.9) | 13 (30.2) | 11 (25.6) | 1.28 | 0.734 |
| Yes | 1 (2.3) | 1 (2.3) | 4 (9.3) | 2 (4.7) | ||
| Cardiovascular disease | ||||||
| No | 2 (4.7) | 8 (18.6) | 13 (30.2) | 11 (25.6) | 0.59 | 0.898 |
| Yes | 1 (2.3) | 2 (4.7) | 4 (9.3) | 2 (4.7) | ||
| Stomach reflux | ||||||
| No | 3 (7) | 9 (20.9) | 13 (30.2) | 8 (18.6) | 3.58 | 0.311 |
| Yes | 0 (0) | 1 (2.3) | 4 (9.3) | 5 (11.6) |
We used a linear regression model for evaluating the effect of study variables on FEV1, FVC, and FEV1/FVC. FEV1, FVC, and FEV1/FVC were dependent variables. At first, we entered all variables in each model. Then we used Fagerland et al. (2013) method to select significant variables.[31] The information of the final three models is shown in Table 4. Shortness of breath was the influential variable on FEV1 (B = -.383 95%CI: -23.729, -12.155 P < 0.001). With regard to beta coefficients when shortness of breath increases, it results in decreasing the level of FEV1. Also shortness of breath was the influential variable on FVC (B = -.296 95%CI: -15.336, -6.082 P < 0.001) and FEV1/FVC (B = -.365 95% CI: -18.362, -9.029 P < 0.001). Beta coefficients indicated that there was a reversed relationship between shortness of breath and FVC as well as FEV1/FVC.
Table 4.
Regression analyses of shortness of breath and lung function indexes (FEV1, FVC, and FEV1/FVC)
| Dependent variable | Independent variables | B | std | β | P | 95,0% Confidence interval for B |
R 2 | |
|---|---|---|---|---|---|---|---|---|
| Lower Bound | Upper Bound | |||||||
| FEV1:** | Shortness of breath | -17.942 | 2.936 | -0.383 | 0.000 | -23.729 | -12.155 | 0.143 |
| FVC:†† | Shortness of breath | -10.709 | 2.348 | -0.296 | 0.000 | -15.336 | -6.082 | 0.083 |
| FEV1/FVC:‡‡ | Shortness of breath | -13.695 | 2.368 | -0.365 | 0.000 | -18.362 | -9.029 | 0.130 |
**Post bronchodilator forced expiratory volume in 1s, ††Post bronchodilator forced vital capacity, ‡‡Post bronchodilator forced expiratory volume in 1s percent in relation to the maximal forced vital capacity
Discussion
This study explored the association of pulmonary symptoms and underlying diseases with spirometry data in smoker adults and in COPD patients. The mean of FEV1 in participants with pulmonary symptoms of shortness of breath, cough, and wheezing was significantly less than participants without symptoms. The mean of FVC in participants with pulmonary symptoms of shortness of breath and cough was significantly less than participants without symptoms. The mean of FEV1/FVC in participants with pulmonary symptoms of shortness of breath, cough, and wheezing was significantly less than participants without symptoms. The shortness of breath was consistently associated with FEV1, FVC, and FEV1/FVC. Whittaker et al.[28] investigated characteristics associated with accelerated decline in a large population of COPD patients over 13 years in a cohort study, which showed breathlessness, high mMRC dyspnea, and mild airflow obstruction were significantly associated with accelerated FEV1 decline. Also characteristics significantly associated with accelerated FVC decline included cough, sputum production, severe airflow obstruction, and history of heart failure. It was recommended that breathlessness should also be considered in assessing lung function progression. Yamane et al.[29] investigated whether the presence of productive cough is a risk factor for the development of COPD during the mean follow-up period of 33.6 20.4 months. The finding showed statistically significant declines in FEV1, %FEV1, and FEV1% during the study period. These findings were supported our result in the present study. Shin et al.[30] examined the relationship between respiratory symptoms and FEV1 in 7518 individuals aged 40–69 years without airflow obstruction based on spirometric testing and in the absence of a medical history of pulmonary disease. The findings suggested that respiratory symptoms included shortness of breath and wheezing are associated with a lower FEV1 in men and nonsmoking women with normal lung function. We found that there was a significant difference between the mean of FEV1 in participants with cardiovascular disease in comparison to those without cardiovascular disease. Silvestre et al.[32] evaluated whether decline in lung function is associated with heart failure, coronary heart disease, and stroke. Among 10,351 participants at about 17 years of follow-up, the result documented that the rapid decline in lung function is associated with a higher incidence of subsequent cardiovascular disease. The other findings of our study were the presence of diabetes mellitus had an inverse association with GOLD COPD severity. In the study of Watz et al.,[33] the frequencies of the metabolic syndrome and consequence hyperglycemia in patients with GOLD stages II, III, and IV were 53, 37, and 44%, respectively. In addition in the study of Quajer et al.,[34] the frequency decreases to about 10% at GOLD stages III and IV. The weight loss that frequently occurs in patients who are in the more severe stages of COPD may be the cause of our observations that association with GOLD COPD severity was inverse.
Conclusion
In conclusion, among pulmonary symptoms, shortness of breath, cough, and wheezing influenced lung function strongly in adult smokers. Moreover, according to the linear regression model, shortness of breath was associated with FEV1, FVC, and FEV1/FVC. Cardiovascular disease could decrease the level of FEV1, whereas diabetic mellitus was associated with milder GOLD COPD severity.
Conflicts of interest
There are no conflicts of interest.
Acknowledgments
The authors thank the staff and participants of this study for their important contributions.
Funding Statement
Nil.
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