European Journal of Cardiovascular Medicine

Chronic obstructive pulmonary disease (COPD) is defined as a heterogeneous lung condition characterised by chronic respiratory symptoms (dyspnoea, cough, and/or sputum production) due to airway (bronchitis, bronchiolitis) and/or alveolar (emphysema) abnormalities that cause persistent, often progressive airflow obstruction [1]. It ranks as the third leading cause of mortality worldwide, with approximately 3.23 million deaths in 2019, and is the seventh leading cause of disability globally [2,3]. Current estimates place the number of individuals living with COPD at more than 400 million, with a global prevalence of 10.6% among adults aged 40 years and older [4].

The global burden of COPD is projected to grow substantially: the estimated number of cases is expected to increase to 592 million by 2050 — a relative increase of 23.3% — driven largely by an ageing global population, increasing female tobacco consumption, and continued household air pollution exposure in low- and middle-income countries (LMICs) [5]. The economic burden is equally staggering: global direct costs amounted to approximately 2.1 trillion USD in 2010, with projections suggesting this figure will double by 2030 [3].

Despite the well-established disease burden, COPD remains substantially underdiagnosed worldwide. Approximately 70% of individuals with COPD have not received a formal diagnosis [5], particularly in resource-limited settings where spirometry is underutilised. Late diagnosis is compounded by the heterogeneity of the disease — which encompasses emphysema, chronic bronchitis, and mixed phenotypes — and the variable clinical presentation across patients with similar spirometric impairment.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) provides the internationally recognised framework for the diagnosis, assessment, and management of COPD. The GOLD report mandates post-bronchodilator spirometry (FEV₁/FVC <0.70) for diagnosis and categorises airflow obstruction severity into four spirometric grades (GOLD 1–4) based on FEV₁% predicted. For treatment guidance, GOLD uses the ABE assessment tool — replacing the former ABCD system — which integrates symptom burden (measured by the modified Medical Research Council dyspnoea scale [mMRC] or COPD Assessment Test [CAT]) with exacerbation history to classify patients into Groups A, B, or E [1,6].

Comprehensive clinical profiling of COPD patients using the GOLD framework — including spirometric grade distribution, symptom burden, exacerbation frequency, and comorbidity mapping — provides essential data to guide individualised therapy and understand real-world disease heterogeneity. Most published profiling studies predate the GOLD revision, and data from South Asian tertiary care settings are particularly limited. This study presents the clinical profile and severity distribution of 320 COPD patients evaluated at a tertiary pulmonology centre using the current GOLD criteria.

This was a cross-sectional observational study conducted at the Department of Pulmonology and Critical Care, Tertiary Care Teaching Hospital. 2.2 Inclusion and Exclusion Criteria Patients aged ≥40 years presenting to the pulmonology outpatient department or inpatient ward with a confirmed diagnosis of COPD were enrolled. Confirmation required: (1) post-bronchodilator FEV₁/FVC <0.70 (fixed-ratio criterion per GOLD); (2) clinical symptoms compatible with COPD (chronic dyspnoea, cough, or sputum); and (3) relevant exposure history. Patients were excluded if they had: (1) an acute exacerbation of COPD within 6 weeks of enrolment; (2) concurrent active pulmonary tuberculosis or malignancy; (3) significant reversibility (>200 mL and >12% improvement in FEV₁ post-bronchodilation) suggesting asthma; or (4) inability to perform acceptable spirometry. 2.3 Clinical Assessment and Data Collection A structured pro forma was used to record: (a) demographic data (age, sex, body mass index [BMI]); (b) exposure history (smoking in pack-years, biomass fuel exposure, occupational dust/fume exposure); (c) symptom duration and presenting complaints; (d) comorbidities; and (e) COPD-related hospitalisation and exacerbation history over the preceding 12 months. Dyspnoea was quantified using the 5-level modified Medical Research Council (mMRC) dyspnoea scale (Grade 0–4; Grade ≥2 indicates significant breathlessness). Health status was assessed using the 8-item COPD Assessment Test (CAT; range 0–40; score ≥10 indicates significant impact). Both tools were administered in the patient's preferred language using validated translations. 2.4 Spirometry and GOLD Grading Post-bronchodilator spirometry was performed using a calibrated Vitalograph spirometer (Vitalograph Alpha Touch, Ireland) in accordance with ATS/ERS technical standards. A minimum of three acceptable manoeuvres were recorded; the best FVC and FEV₁ were used. Reference values were derived from GLI-2012 equations adjusted for ethnicity. GOLD spirometric grades were assigned based on FEV₁% predicted (post-bronchodilator) in patients with confirmed FEV₁/FVC <0.70: Table 1. GOLD Spirometric Grading System (GOL) GOLD Grade Severity FEV₁ % Predicted Clinical Implication 1 Mild ≥ 80% Airflow limitation with symptoms; often undiagnosed 2 Moderate 50–79% Progressive dyspnoea; medical attention sought 3 Severe 30–49% Worsening dyspnoea; frequent exacerbations; reduced quality of life 4 Very Severe < 30% Chronic respiratory failure; high mortality risk FEV₁ = forced expiratory volume in 1 second. Source: GOLD 2021 Global Strategy for COPD. 2.5 ABE Assessment Tool The GOLD ABE assessment tool (introduced in GOLD and retained in 2021) replaces the former ABCD system. Patients are assigned to Groups A, B, or E based on two parameters: (1) symptom burden (mMRC 0–1 or CAT <10 = low symptoms; mMRC ≥2 or CAT ≥10 = high symptoms); and (2) exacerbation history in the preceding 12 months (Group E = ≥2 moderate exacerbations or ≥1 hospitalisation; Groups A and B = 0 or 1 moderate exacerbation without hospitalisation). Groups A and B are differentiated solely by symptom burden [1]. 2.6 Statistical Analysis Data were entered and analysed using IBM SPSS v26.0. Continuous variables are presented as mean ± standard deviation (SD) or median (interquartile range [IQR]); categorical variables as frequencies and percentages. Pearson correlation coefficients were computed to assess relationships between CAT/mMRC and spirometric variables. Chi-square tests were used for categorical comparisons across GOLD groups. One-way ANOVA with Tukey post-hoc testing was applied for continuous inter-group comparisons. A p-value <0.05 was considered statistically significant.

3.1 Demographic and Baseline Characteristics

A total of 320 patients with spirometry-confirmed COPD were enrolled during the study period. Baseline demographic and clinical characteristics are summarised in Table 2.

The mean age was 62.4 ± 9.8 years (range: 42–84 years). Males constituted 74.1% (n=237) of the cohort. Body mass index (BMI) was 22.6 ± 3.8 kg/m². The mean duration of respiratory symptoms prior to confirmed diagnosis was 7.2 ± 4.6 years, indicating a substantial diagnostic delay.

Cigarette smoking was the predominant risk factor (76.6%; mean 38.4 ± 14.2 pack-years). Biomass fuel exposure (cooking or heating) was present in 18.4%, predominantly among female patients (p<0.001). Occupational dust or fume exposure was reported in 24.1%. A family history of COPD or chronic lung disease was present in 21.3%.

Table 2.  Baseline Demographic and Clinical Characteristics of the Study Population (n=320)

BMI = body mass index; BD = bronchodilator; SpO₂ = peripheral oxygen saturation by pulse oximetry; IQR = interquartile range.

3.2 GOLD Spirometric Grade Distribution

The distribution of patients across GOLD spirometric grades is shown in Table 3 and illustrated in Figure 1. The largest proportion of patients presented with GOLD Grade 2 (moderate: FEV₁ 50–79% predicted), accounting for 43.1% of the cohort. GOLD Grade 3 (severe) was present in 29.7%, GOLD Grade 1 (mild) in 16.3%, and GOLD Grade 4 (very severe) in 10.9%. Combined, 82.8% of patients had moderate-to-very severe airflow obstruction (GOLD Grades 2–4) at the time of assessment.

The mean FEV₁% predicted declined progressively and significantly across grades (p<0.001): Grade 1: 87.4 ± 5.1%; Grade 2: 63.8 ± 8.7%; Grade 3: 38.4 ± 6.2%; Grade 4: 21.7 ± 4.9%. Total lung capacity (TLC) and residual volume/total lung capacity (RV/TLC) ratio increased significantly with higher grades, consistent with progressive hyperinflation.

3.3 Symptom Assessment: mMRC and CAT Scores

The mean CAT score for the entire cohort was 18.9 ± 7.4, and 71.3% of patients had a CAT score ≥10 (indicating significant health status impairment). The mean mMRC grade was 2.2 ± 1.1, with 61.6% having mMRC ≥2 (indicating significant breathlessness). Discordance between the two tools was observed in 22.5% of patients: 11.6% had mMRC <2 but CAT ≥10, and 10.9% had CAT <10 but mMRC ≥2.

Table 3.  GOLD Spirometric Grade Distribution and Spirometric Parameters

All values mean ± SD unless stated. FEV₁ = forced expiratory volume in 1 second; CAT = COPD Assessment Test (range 0–40); mMRC = modified Medical Research Council dyspnoea scale (range 0–4).

CAT score correlated more strongly with FEV₁% predicted (r = –0.62, p<0.001), exacerbation frequency (r = 0.55, p<0.001), and comorbidity count (r = 0.51, p<0.001) than mMRC. The mMRC-FEV₁ correlation was weaker (r = –0.48, p<0.001). These findings are consistent with the broader literature demonstrating the multidimensional superiority of CAT over mMRC for overall COPD impact assessment [7,8].

3.4 GOLD ABE Group Distribution

Using the GOLD ABE assessment tool, the distribution was as follows: Group A (low symptoms, 0–1 non-hospitalising exacerbations): 91 patients (28.4%); Group B (high symptoms, 0–1 non-hospitalising exacerbations): 113 patients (35.3%); Group E (≥2 moderate exacerbations or ≥1 severe/hospitalising exacerbation): 116 patients (36.3%). Mean FEV₁, CAT, and mMRC values across ABE groups are shown in Table 4.

Table 4.  GOLD ABE Group Distribution and Key Parameters

Group E: ≥2 moderate exacerbations or ≥1 hospitalisation for exacerbation in preceding 12 months. Groups A and B: 0 or 1 moderate exacerbation without hospitalisation, differentiated by symptom burden.

3.5 Exacerbation History

The mean number of exacerbations in the preceding 12 months was 1.8 ± 1.4. Of 116 Group E patients, 68 (58.6%) had ≥2 moderate exacerbations requiring antibiotic and/or oral steroid treatment, and 48 (41.4%) had at least one severe exacerbation requiring hospital admission. The frequency of exacerbations was strongly associated with GOLD spirometric grade (p<0.001): Grade 1 patients reported a mean of 0.4 ± 0.7 exacerbations/year, compared with 3.1 ± 1.7 in Grade 4 patients.

Among Group E patients, 31.0% had a history of intensive care unit (ICU) admission for COPD-related respiratory failure in the preceding 24 months. Non-invasive ventilation (NIV) had been used in 18.6% of the total cohort. These figures indicate substantial hospitalisation burden in the more severely affected subgroups.

3.6 Comorbidity Profile

Comorbidities were documented in 86.3% of patients (at least one comorbid condition). The comorbidity profile is summarised in Table 5 and reflects the well-established cardiovascular and metabolic multimorbidity burden of COPD. The most prevalent comorbidities were hypertension (38.1%), ischaemic heart disease (22.5%), diabetes mellitus type 2 (18.4%), anxiety and/or depression (16.6%), and cor pulmonale (14.7%). The mean number of comorbidities was 2.1 ± 1.3 per patient and increased significantly with GOLD grade (p<0.001).

Table 5.  Comorbidity Profile (n=320)

*Association with GOLD grade based on chi-square analysis (p<0.05). ICS = inhaled corticosteroids; CT = computed tomography.

3.7 Pharmacological Treatment at Enrolment

At the time of enrolment, 57.8% of patients were on some form of bronchodilator therapy. However, 22.8% were receiving only short-acting bronchodilators (SABAs or SAMAs) despite moderate or severe airflow obstruction, representing suboptimal treatment alignment with GOLD recommendations. Long-acting bronchodilator therapy (LABA or LAMA monotherapy) was used in 28.4%, and dual long-acting bronchodilator therapy (LABA+LAMA) in 18.1%. Triple therapy (ICS/LABA/LAMA) was prescribed in 11.3%, predominantly in Group E patients. Notably, 42.2% had not been formally diagnosed or treated prior to this visit — further confirming the underdiagnosis gap in the study population.

This cross-sectional study provides a detailed clinical profile of 320 COPD patients assessed using the GOLD criteria at a tertiary care pulmonology centre in South India. The findings reveal several important patterns in disease presentation, severity distribution, and clinical management that have direct implications for healthcare delivery.

4.1 Late Presentation and Diagnostic Delay

A striking finding is that 82.8% of patients presented with GOLD Grade 2 or worse, with a mean symptom duration exceeding 7 years before diagnosis. This pattern of late presentation is consistent with global data showing that approximately 70% of COPD cases remain undiagnosed, particularly in LMICs where spirometry is underutilised in primary care [5]. The diagnostic gap is compounded by the insidious progression of COPD — patients often attribute early dyspnoea and cough to ageing or smoking, delaying medical consultation.

Earlier diagnosis, particularly at GOLD Grade 1, would allow earlier institution of smoking cessation, pulmonary rehabilitation, vaccination, and pharmacotherapy — all of which have proven benefits in modifying the natural history of COPD. The integration of spirometry into routine primary care encounters, lung cancer CT screening programmes, and occupational health checks represents a key strategy to shift the diagnostic profile towards milder disease stages [1,9].

4.2 Spirometric Grade Distribution

The predominance of Grade 2 (43.1%) followed by Grade 3 (29.7%) is consistent with tertiary referral centre profiles reported in comparable Indian and South Asian studies [10]. The relatively small proportion at Grade 1 (16.3%) reflects both the diagnostic delay phenomenon and the referral filter effect — patients with mild disease are less likely to be referred for specialist evaluation. The progressive decline in FEV₁ across grades was statistically significant, validating the grading system's ability to stratify physiological impairment within this cohort.

It is, however, important to acknowledge the known limitations of FEV₁ as a sole severity marker. FEV₁ is only weakly predictive of symptom burden, exercise capacity, and quality of life at the individual patient level [7]. This is precisely why the GOLD ABE tool was developed — to complement spirometric grading with symptom and exacerbation data in treatment decision-making.

4.3 ABE Group Distribution: High Symptom and Exacerbation Burden

The distribution across ABE groups (A: 28.4%; B: 35.3%; E: 36.3%) indicates that over 70% of the cohort had either significant symptom burden or high exacerbation risk at enrolment. Group E (36.3%) is of particular clinical concern: these patients require intensified pharmacotherapy (dual bronchodilation or triple therapy), pulmonary rehabilitation, and structured follow-up. The high proportion of Group E patients — particularly those with prior hospitalisations — reflects the advanced disease stage at presentation characteristic of tertiary referral populations.

The transition from the ABCD to the ABE system in GOLD was intended to de-emphasise spirometric grade from the treatment algorithm and instead focus clinicians on the two most treatment-responsive characteristics: symptoms and exacerbations [6]. Our data support this approach: Group B and Group E patients had substantially higher CAT scores and exacerbation frequencies than Group A, regardless of spirometric grade, reinforcing the importance of multidimensional assessment.

4.4 CAT vs. mMRC: Superiority of CAT for Multidimensional Assessment

A key finding is that CAT demonstrated stronger correlations with spirometric parameters, exacerbation frequency, and comorbidity burden than mMRC. Discordance between the two tools (22.5%) is consistent with published data showing misclassification rates of 13–38% when patients are categorised using one tool versus the other [8,11]. The mMRC measures only a single dimension — dyspnoea — whereas CAT captures cough, sputum, chest tightness, activity limitation, sleep disruption, and confidence. For a disease as multidimensional as COPD, the CAT's broader scope provides a more comprehensive and accurate patient-level severity assessment [7].

These findings support the practical recommendation to use both tools in combination in clinical settings where time permits, and to preferentially use CAT when a single instrument must be chosen — particularly in patients with high symptom burden in whom mMRC might underestimate disease impact.

4.5 Comorbidity Burden

The high prevalence of comorbidities — particularly hypertension (38.1%), ischaemic heart disease (22.5%), and diabetes mellitus (18.4%) — reflects the systemic inflammatory and metabolic consequences of COPD and the shared risk factor of tobacco smoking. Comorbidities in COPD are not merely coincidental: they independently influence prognosis, exacerbation risk, hospitalisation, and mortality [1]. Depression and anxiety (16.6%) deserve particular attention, as they worsen treatment adherence, physical activity, and health-related quality of life, yet remain systematically underdiagnosed and undertreated in respiratory clinics.

Cor pulmonale (14.7%) and bronchiectasis (11.9%) were predominantly seen in Grades 3–4 and Group E respectively, highlighting that structural comorbidities emerge and compound morbidity in advanced COPD. The presence of concurrent lung cancer in 4.4% of patients — all in Grades 3–4 and heavy smokers — underscores the importance of low-dose CT screening in this high-risk subgroup.

4.6 Treatment Gaps

The finding that 42.2% of patients had not previously been formally diagnosed or treated — and that 22.8% of those already known to have COPD were receiving suboptimal short-acting bronchodilator-only regimens — indicates a significant treatment gap. GOLD clearly recommends long-acting bronchodilators as the pharmacological cornerstone of stable COPD management from Group B onwards, with escalation to dual bronchodilation for Group E and consideration of triple therapy (ICS/LABA/LAMA) in Group E patients with eosinophil count ≥300 cells/µL or concurrent asthma overlap [1]. Bridging this prescribing gap requires clinician education, healthcare system capacity building, and improved access to inhaled therapies.

4.7 Limitations

This study has several limitations. First, as a single-centre cross-sectional study from a tertiary referral centre, the findings may not be representative of COPD patients in primary care or the community, where milder disease predominates. Second, blood eosinophil counts were not consistently available for all patients, precluding full integration of this biomarker into treatment stratification analysis. Third, validated tools such as the six-minute walk test and St. George's Respiratory Questionnaire were not systematically administered. Fourth, cross-sectional design limits inferences about disease progression, treatment response, and mortality outcomes. Longitudinal follow-up studies are warranted to address these gaps.

This study provides a comprehensive clinical profile of COPD patients using the GOLD framework in a tertiary care setting. The majority of patients presented with moderate-to-severe airflow obstruction, substantial symptom burden, and high exacerbation risk — reflecting both the late-diagnosis paradigm and the referral filter effect. The predominance of Group B and Group E classifications underscores the urgent need for multidimensional assessment beyond spirometry alone. CAT demonstrated superior performance to mMRC in capturing overall COPD severity, correlating more strongly with spirometric grade, exacerbation frequency, and comorbidity burden. The high comorbidity prevalence — particularly cardiovascular disease and depression — highlights COPD as a systemic disease requiring holistic, multidisciplinary management. Significant treatment gaps were identified, with over 40% of patients previously undiagnosed and nearly one-quarter on suboptimal regimens. These findings call for: (1) expanded spirometric screening to enable earlier diagnosis; (2) universal adoption of the GOLD ABE assessment tool in routine clinical practice; (3) integration of both CAT and mMRC for complete symptom profiling; (4) proactive screening and treatment of comorbidities; and (5) guideline-concordant pharmacotherapy aligned with ABE group classification. Implementation of these strategies has the potential to meaningfully reduce the morbidity, healthcare utilisation, and mortality burden of COPD in South Asian and global populations.

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