Chronic Obstructive Pulmonary Disease (COPD) is a diverse lung condition marked by chronic symptoms like dyspnea, cough, and sputum production, resulting from airway and alveolar abnormalities that lead to persistent airflow obstruction.^[1] The World Health Organization (WHO) identifies COPD as a leading global cause of death, often linked to tobacco smoking, although many patients have never smoked. Approximately 3 billion people are exposed to biomass fuel smoke, a significant risk factor for COPD, especially in developing countries, where around 50% of COPD-related deaths are attributed to biomass smoke, affecting mainly women. A study in Turkey found a 23% prevalence of COPD among never-smoking women exposed to biomass smoke.^[2]

Chronic airway inflammation and obstruction in asthma can lead to airway wall thickening and fibrosis, potentially resulting in irreversible airflow limitation and COPD. COPD is diagnosed with non-fully reversible airflow limitation (FEV1/FVC < 0.7 post-bronchodilation) via spirometry. Preserved ratio impaired spirometry (PRISm) is characterized by reduced FEV1 (< 80% of predicted) with a preserved FEV1/FVC ratio (≥ 0.7), with a prevalence of 3 to 20%.^[3]

Prism is a risk factor for developing COPD, along with increased respiratory symptoms and mortality. ^[3-8] Research indicates that small airways under 2mm in diameter are the primary site of airflow obstruction in COPD.^[9] Micro-computed tomography (micro-CT) reveals that reductions in terminal and transitional bronchioles occur before visible emphysematous destruction or meeting spirometric criteria for COPD, highlighting its role as a risk factor. Knowledge about non-smoking risk factors for COPD in India remains limited.^[10]

While smoking is a well-established risk factor, other contributors include exposure to air pollutants, workplace dust and fumes, repeated childhood respiratory infections, pulmonary tuberculosis, chronic asthma, intrauterine growth retardation, poor nutrition, and low socioeconomic status. The NHANES III study found a 6.6% prevalence of COPD among never-smokers, diagnosing it with post-bronchodilator spirometry (FEV1/FVC ratio <0.70). ^[11,12]

About 50% of deaths from COPD in developing countries are attributable to biomass smoke, of which about 75% are of women.^[2] The prevalence of airflow obstruction varies from 28% to 68% of patients with pulmonary tuberculosis.^[13] In a study of fully treated patients attending for routine follow-up, the proportion with airflow obstruction was 48% ^[14]; the proportion increased with duration since treatment completion, but age was not a confounding factor. Poorly treated chronic persistent asthma or severe asthma can cause changes in the lungs that are like those resulting from smoking.^[15]

OBJECTIVES

• To estimate the prevalence of COPD in non-smoking females over the age of 40 years with chronic respiratory symptoms.
• To identify the association of COPD with risk factors such as exposure to biomass fuel, occupational exposure to dust and fumes, history of pulmonary tuberculosis, childhood respiratory infections, and exposure to outdoor and indoor air pollution.
• To identify non-smoking females who are at risk of developing COPD by identifying spirometric abnormalities which are small airway obstruction and non-restricted PRISm.
• To identify the characteristics of non-smoking females with COPD, such as Body Mass Index, symptom burden with COPD-PS score, mean age at presentation, and severity of airflow obstruction (FEV1).

Study design and setting:

This cross-sectional study was conducted over six months from October to February 2024 in the Department of Respiratory Medicine of a tertiary care teaching hospital after obtaining approval from the institutional ethics committee (IEC No.: IEC/MAMS/2023/021).

Study population:

INCLUSION CRITERIA: The study population included women over the age of 40 who are never smokers and who as per CDC guidelines have smoked less than 100 cigarettes in their lives.

EXCLUSION CRITERIA: The study population excluded active smokers, those who have had a clinical diagnosis of asthma; individuals with a history of acute wheeze, breathlessness, or deterioration associated with allergens; individuals with significant bronchiectasis, inflammatory bowel disease, rheumatoid arthritis, and chest wall deformity; those who are contraindicated for pulmonary function testing and participants with a serious life-threatening illness.

Sample size:

The sample size was calculated as 75, by using the given formula: n = (z)² p (1 – p) / d²   

taking the prevalence of COPD among non-smoker females as 23%

1.96*1.96*23*77/10*10 = 6803/100 = 68.03

68+ 10% non-response rate =75

Data collection:

All female patients over the age of 40 years, visiting Respiratory Medicine OPD with complaints of cough/ sputum production and shortness of breath for more than 1 year are included in the present study.

The study began with taking a history regarding symptoms and risk factors after obtaining informed consent from the patient followed by the COPD PS questionnaire. The COPD Population Screener (COPD-PSTM; Quality Metric Incorporated, Lincoln, Rhode Island, USA) is a validated, self-scored, 5-item questionnaire, used to identify patients at risk for COPD. It includes three questions (dyspnea, sputum production, and activity limitation) related to COPD and questions regarding smoking and age. It can be used as a first-level screener in diagnosing airflow obstruction reliably. ^[16,17]

According to the GOLD criteria, spirometry is the gold standard diagnostic measure for confirming COPD. The device used to perform spirometry was Easy One Connect ultrasonic flow sensing spirometer (Figure A). Spirometry was performed by asking the patients to take a deep breath with the mouth placed tightly around the mouthpiece, followed by a full expiration for at least 6 seconds into the mouthpiece. A diagnosis of COPD was made if the post-bronchodilator forced expiratory volume in one second (FEV1) is <80% of the predicted value in combination with an FEV1/Forced vital capacity (FVC) ratio of <70%^[1]. Preserved ratio impaired spirometry (PRISm) is defined by reduced FEV1 (< 80% of predicted value) with a preserved FEV1/FVC ratio (≥ 0.7). PRISm can be divided into two groups according to the presence or absence of a restrictive abnormality (FEV1/ FVC ≥ 0.7 and FVC < 80% predicted).^[3-6] Individuals with PRISm were classified according to the presence or absence of restrictive abnormality; these groups were non-restrictive PRISm (FEV1/FVC ≥ 0.7, FEV1 < 80% and FVC ≥ 80%) and restrictive PRISm (FEV1/FVC ≥ 0.7, FEV1<80%andFVC<80%).^[18] Small airway obstruction is defined by reduced FEF25-75(<65% predicted).

FIGURE A SPIROMETER

The collected data comprised of FEV1/FVC ratio, FEV1, FVC, FEF25-75, BMI, COPD PS score, symptoms and risk factors was tabulated.

Data Analysis:

Data analysis was conducted using Microsoft Excel and IBM SPSS Statistics 27. A p-value <0.05 was considered significant.

100 patients who have symptoms of cough with sputum production, shortness of breath, and exacerbations for more than one year are included in the present study. COPD PS score was calculated, and spirometry was performed. 15 patients who performed poor-quality spirometry and did not fit the adequacy criteria were excluded from the current study. 56 out of 70 have PRISm and 14 have restrictive abnormality.  

Figure 1: Distribution as per presence or absence of COPD (n=85)

From Figure 1, It was observed that 15% of the study subjects have COPD.

Figure 2: Distribution of all the participants according to their spirometry(n=85)

From Figure 2, of 85 participants, 2 had normal spirometry and the rest 83 had spirometric abnormalities.13 participants have COPD as defined by spirometry criteria: FEV1/FVC < 0.7. 70 participants did not fit the spirometric criteria for COPD and had FEV1/FVC > 0.7.

Figure 3: Distribution according to type of PRISM (n=56)

Figure 3 shows that 94.6% of the study subjects had restrictive PRISM, whereas only 5.35% had Non-restrictive PRISM. PRISm is further classified into restrictive PRISm(FEV1/FVC> 0.7, FEV1<80%, FVC<80%) and non-restrictive PRISm(FEV1/ FVC> 0.7, FEV1<80%, FVC>80%). 3 out of 56 have non-restrictive PRISm and 53 have restrictive PRISm.

Table 1: Distribution of study subjects according to mean BMI in various categories

The mean age of the population is 51.27 + 11.87. The mean age of COPD patients is 54.15+ 14.03. The mean age of patients with non-restrictive PRISM is 51.27 + 15.14, restrictive PRISM is 54.33 + 10.34. The BMI of the COPD population is 27.13+ 7.71. The average BMI of patients with non-restrictive PRISM is 25.7 + 3.84 and those with restrictive PRISM are 28.03 + 6.43. Table 1. The mean COPD PS score of the total population is 2.48 + 0.56. The COPD population has a mean COPD PS score of 3.23 + 0.44. The average COPD PS score of the PRISm population is 2.93 + 0.48. The participants with non-restrictive PRISm all have a COPD PS score of 3; out of the participants with restrictive PRISm,18 have a score of 2, and 35 have a score of 3.

Figure 4: Small Airway Obstruction distributed among COPD and PRISm patients.

Out of 85 participants, 48 have small airway obstruction. All participants with COPD(n=13) and non-restrictive PRISM(n=3) have small airway obstruction.

Table 2: Distribution of study subjects according to exposures and COPD-PS score (n=85)

In this study biomass fuel exposure was present in 10 out of 13 COPD patients, exposure to dust and fumes was present in 2 out of 13, and 3 out of 13 had a history of recurrent childhood respiratory infections. All 3 participants with non-restrictive PRISM were exposed to biomass fuel and 1 of the 3 also had a history of pulmonary tuberculosis. Out of the 32 patients with only small airway obstruction as spirometric abnormality, exposure to biomass fuel was present in 27, exposure to dust and fumes was present in 5 and recurrent childhood respiratory infections were present in 15.

Table 3: Symptom burden among study subjects (n=85)

Table 3. In the present study out of 15.29% who have COPD, 30.77% have cough, shortness of breath, and wheeze as their symptoms, and 69.23% have cough and shortness of breath. Of the remaining 84.74% who do not have COPD, 41.66% have cough and shortness of breath, 43.05% have only shortness of breath, and the remaining have wheeze.

Table 4: Association between COPD-PS and FEV1/FVC ratio among study subjects (n=85)

The results show a significant association between a higher COPD severity score (as indicated by the COPD-PS) and the FEV1/FVC ratio. Most individuals with a lower COPD-PS (<3) tend to have a higher FEV1/FVC ratio (indicating better lung function), while those with a higher COPD-PS (>3) are more likely to have an FEV1/FVC ratio of <0.7, which reflects more obstructed or impaired lung function.

In this study, 56.24% have a spirometric abnormality that is either diagnostic of COPD or puts them at an increased risk of developing COPD in the future [in the form of non-restrictive PRISm or small airway disease]. ^[3-8,19] In this study, the prevalence of COPD in non-smoking females is 15.29%, which is slightly higher than that in male smokers. In a prospective study by Al Omari M et al the prevalence of COPD was found to be 8.2% in male smokers. ^[19] Khassawneh B et al found the prevalence of COPD to be 12.5% in male smokers in Jordan ^[20]. In the Rotterdam study, the overall prevalence of COPD in male and female smokers was 13.6%.^[21]

In the current study, the mean COPD-PS score of patients with COPD is 3.23 ± 0.44, which is higher than the mean COPD-PS score of the total population, 2.48 ± 0.56, reflecting an increased symptom burden in the COPD population. In this study, a COPD-PS score of greater than or equal to 3 is found to be statistically significant in screening patients for COPD(p=0.0001). Gu Y et al reported that a COPD-PS score of 5.03 ± 5.11 is statistically significant in screening male smokers with COPD (p < 0.001) and that at a cut-off of 4, the sensitivity and specificity of COPD-PS for identifying COPD is 74.52% and 70.24%, respectively ^[22] indicating that non-smoking women with COPD have comparatively lower symptom burden than male smokers with COPD. This could cause delays in seeking medical attention and continued exposure to risk factors such as biomass fuel, dust and fumes, indoor and outdoor air pollutants, and other irritant gases. Timely detection of COPD helps in sensitization of the patient to these risk factors so that the progression of COPD from further exposure could be limited.

According to this study, the mean FEV1 at the initial presentation of all the female COPD patients was 1.1L (47.92% + 8.65 predicted), this value falls within the range indicative of severe COPD (GOLD STAGE III) as per GOLD staging and the mean age at presentation is 54.15 + 14.03. In the natural history of chronic airflow obstruction Fletcher and Peto demonstrated that when airflow obstruction first causes breathlessness that leads a patient to consult a -doctor, it is usually sufficiently severe to reduce the forced expiratory volume in one second (FEV1) to about 1 liter, which is less than half the normal value. In the study of R Kessler et al three-hundred and forty-two symptomatic COPD patients (57% of the eligible) were studied (93% males). Their mean FEV1 was found to be 54% (moderate obstruction on gold staging). ^[16] In a study of 47 COPD patients (93.6% male smokers) who presented with symptoms to the hospital for the first time, Previous research reported a mean FEV1 of 51.77 + 13.64% predicted; moderate obstruction (GOLD STAGE II at a mean age of 63.5 years.^[16]. This analysis concludes that nonsmoking females exposed to risk factors for COPD predominantly biomass fuel, exhibit a higher susceptibility and typically demonstrate poorer lung Function compared to male smokers at the time of their initial presentation to the hospital. Similar findings were observed among females affected with smoking-related COPD. A systematic review of 11 studies demonstrated that female smokers had a faster annual decline in FEV1 than male smokers, even when they smoked fewer cigarettes. Overall, female smokers have about a 50% higher chance of developing COPD than men.^[24] This study also implicates that risk factors other than smoking such as biomass fuel are equally potent if not more in causing accelerated decline in lung function thereby causing severe COPD. The mean BMI of COPD patients from this study was found to be 27.13, which is similar to the BMI of COPD patients obtained in other studies.^[26] Salma Mokaddem Mohsen et al reported a mean BMI of 26.4 and concluded that a BMI of less than 18.5 accelerates evolution toward poorer lung function in COPD and obesity seems to be a protective factor for COPD patients.^[25] Male and female smokers have a significantly lower BMI when compared to their nonsmokers and ex-smoker counterparts. In contrast, female smokers with COPD have a significantly lower BMI_.^[26] In the current study, we identified biomass fuel as a major risk factor associated with the development of COPD. 69.23% of patients with COPD had biomass fuel exposure followed by a history of recurrent childhood infections and exposure to indoor and outdoor pollutants. Despite Pulmonary tuberculosis being a prevalent risk factor for COPD development in India,^[8] None of this study participants with COPD had a history of pulmonary tuberculosis. Prism is reported to be a risk factor in the development of COPD. ^[3-8] In the current study, 56 out of 85 participants were identified as having PRISm. 5.35% of the PRISm population have non-restrictive PRISm, while the remaining 94.6% have restrictive PRISm. Longitudinal analysis of lung function showed that non-restrictive PRISm, but not restrictive PRISm, was independently associated with the development of airflow obstruction. ^[3-8] This concludes that 3.52% of this study population (non-restrictive PRISm) are at risk for developing COPD shortly. Within the study population, 56% [n=48] of individuals were found to have small airway obstruction. Notably, all patients diagnosed with COPD demonstrated small airway obstruction (27.08%, n=13). 6.25% displayed both small airway obstruction and non-restrictive PRISm, potentially indicating a higher risk of developing COPD in the future. The remaining 66.66% of patients demonstrated small airway obstruction as the only spirometric abnormality. It is now well established that the small conducting airways (<2mm in diameter) become the major site of airflow obstruction in COPD and that small airway disease is an early pathological feature in mild and moderate COPD.^[10] It is noteworthy that COPD is associated with Indoor air pollution and tends to exhibit a higher prevalence of small airway disease than emphysema, in contrast to what is typically observed in cigarette smokers.^[26] The reasons behind the greater susceptibility of women to develop COPD with small airway disease predominance are largely unknown. This may be due to the airways of females being relatively smaller than those of males for the same lung volume, so there may be a greater concentration of smoke per unit area of a small airway surface.^[24]

Non-smoking females with COPD present at a younger age as compared to male smokers and have poorer lung function (FEV1) at the time of initial presentation indicating severe airflow obstruction. They also have a lower symptom burden which may lead to a delay in recognition of symptoms by patients and continued exposure to risk factors increasing mortality.

LIMITATIONS

The number of patients examined was limited to 85. A study with a larger population can accurately predict the prevalence of COPD in nonsmoking females. Spirometry, as a diagnostic test, relies heavily on patient cooperation and effort. In instances of inadequate patient compliance, inaccurate test results may be obtained, which cannot be evaluated resulting in less data available for statistical analysis.

Risk factors other than smoking, notably Biomass fuel Exposure, Indoor and outdoor pollutants, recurrent childhood Respiratory infections, history of Tuberculosis, and Exposure to dust and fumes contribute significantly to the development of COPD in females. Recognition of risk factors other than smoking that cause COPD and utilization of spirometry to make accurate diagnoses for a timely intervention will reduce the mortality and morbidity in females at risk of developing COPD.

RECOMMENDATIONS: Promote environmental interventions to reduce exposure to pollutants, second-hand smoke, and occupational risks that contribute to COPD in non-smokers. Implement screening programs for non-smoking females at high risk (e.g., asthma history, environmental or occupational exposure) to detect COPD and small airway dysfunction early.

Funding: ICMR

Conflicts of interest: None

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