European Journal of Cardiovascular Medicine

Chronic obstructive pulmonary disease (COPD) is a progressive, irreversible respiratory disorder characterized by airflow limitation, primarily caused by smoking, environmental exposure, and chronic airway inflammation ¹. Globally, COPD is the third leading cause of death and contributes significantly to healthcare costs ². Acute exacerbations (AECOPD) are defined as sudden worsening of respiratory symptoms—mainly dyspnea, cough, and sputum production—requiring changes in regular medication ³.

Exacerbations accelerate lung function decline, impair quality of life, and increase mortality ⁴. Bacterial infections are implicated in nearly 50–70% of cases ⁵, making antimicrobial therapy an integral component of management. Common pathogens include Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae ⁶. Rational antibiotic selection is crucial to ensure efficacy while limiting resistance ⁷.

Macrolides and Tetracyclines are frequently used due to their broad coverage, anti-inflammatory properties, and safety ⁸. Azithromycin, a macrolide, offers excellent tissue penetration and prolonged post-antibiotic effect ⁹. It reduces neutrophil-mediated inflammation and bacterial load, thereby improving symptoms and preventing recurrent exacerbations ¹⁰. Doxycycline, a long-acting tetracycline derivative, also exhibits anti-inflammatory actions by inhibiting metalloproteinases and cytokine release ¹¹.

Several studies have evaluated these antibiotics individually; however, head-to-head comparisons in AECOPD remain limited ¹²,¹³. Moreover, the emergence of macrolide resistance underscores the need for evidence-based antibiotic selection ¹⁴. The present study aims to comparatively evaluate the clinical efficacy, spirometric improvement, and safety profile of azithromycin versus doxycycline in patients with acute exacerbations of COPD

This is a prospective and comparative study, conducted by Department of Respiratory Medicine and Pharmacology at Sapthagiri Institute of Medical Sciences and Research Centre, Bengaluru, Karnataka from August 2024 to July 2025. Patients were allocated to the groups by chits method.

Odd numbered patients were included in group A and were Azithromycin 500mg orally once daily for 3 days and even numbered patients were included in group B and were given Doxycycline 100mg orally twice daily for 5 days.Both the groups received standard therapy according to Global initiative for Chronic Obstructive Lung Disease(GOLD) guidelines.

Inclusion Criteria

1. Adults aged ≥ 40 years
2. Clinically diagnosed COPD (as per GOLD 2024 guidelines)
3. Presentation with moderate-to-severe acute exacerbation
4. Patients willing to give written informed consent.

Exclusion Criteria

• Co-existing pneumonia or bronchiectasis
• History of recent antibiotic use (< 14 days)
• Severe hepatic/renal impairment
• Known hypersensitivity to macrolides or tetracyclines
• Pregnant or lactating women

Outcome Measures

1. Symptom score (dyspnea, sputum volume/purulence)
2. FEV₁ (L) improvement post-therapy
3. Duration of hospital stay
4. Clinical success at Day 7
5. Incidence of ADRs

Symptom Score Assessment

1. Dyspnea Score:
   Dyspnea severity was graded using the Modified Medical Research Council (mMRC) Dyspnea Scale, which ranges from 0 to 4, where:
   1. Grade 0: Breathless only with strenuous exercise
   2. Grade 1: Short of breath when hurrying on level ground or walking up a slight hill
   3. Grade 2: Walks slower than people of the same age on level ground due to breathlessness or has to stop for breath while walking at own pace
   4. Grade 3: Stops for breath after walking ~100 meters or after a few minutes on level ground
   5. Grade 4: Too breathless to leave the house or breathless when dressing/undressing

Improvement was calculated as the difference between baseline and Day 7 scores.

2. Cough Severity:
   Cough was assessed using a 5-point Cough Severity Scale (CSS) adapted from the Leicester Cough Questionnaire (LCQ):
   1. Score 0: No cough
   2. Score 1: Occasional cough, not troublesome
   3. Score 2: Frequent cough, mildly troublesome
   4. Score 3: Persistent cough interfering with daily activity
   5. Score 4: Severe cough disturbing sleep and daily function

The change in cough score (ΔCSS) from baseline to Day 7 was recorded to evaluate therapeutic response.

Statistical Analysis

Data were analyzed using SPSS v26. Continuous variables were compared using Student’s t-test; categorical variables with Chi-square test. p < 0.05 was considered significant.

Table 1: Demographic Distribution

Table 2: Baseline Clinical Characteristics

Table 3: Post-Treatment Symptom Improvement

Table 4: Spirometric Changes (FEV₁ in L)

Table 5: Clinical Outcome and Hospital Stay

Table 6: Adverse Drug Reactions

This study demonstrates that both azithromycin and doxycycline are effective for managing AECOPD, with azithromycin showing a faster clinical recovery and shorter hospital stay. These results align with the anti-inflammatory and pharmacokinetic advantages of azithromycin observed in previous studies ¹⁵–¹⁸.

The mean improvement in FEV₁ (0.32 L vs 0.25 L) in our study mirrors findings by Hanania et al. (2020) ¹⁹, who reported enhanced lung function and reduced hospitalization with macrolide therapy. The shorter duration of therapy (3 days) for azithromycin may enhance adherence compared to doxycycline’s 5-day regimen. Both agents were well tolerated, though doxycycline caused mild photosensitivity in a few cases, consistent with Sethi et al. (2018) ²⁰.

Macrolides also possess immunomodulatory effects beyond antimicrobial action, reducing airway cytokines and neutrophilic inflammation ²¹. Long-term azithromycin use has been associated with decreased exacerbation frequency, as demonstrated by Albert et al. (2019) ²². However, concerns about macrolide resistance and QT prolongation remain ²³. Doxycycline, being inexpensive and safe, remains an excellent alternative, especially in regions with high resistance or cardiac risk ²⁴.

Our study was limited by its single-center design, small sample size, and short follow-up. Future multicentric trials should assess microbiological outcomes and resistance patterns.

Overall, this comparative evaluation highlights that azithromycin offers superior short-term recovery, while doxycycline remains a cost-effective and well-tolerated option.

Both azithromycin and doxycycline are effective in treating AECOPD.
Azithromycin demonstrated faster clinical recovery, greater FEV₁ improvement, and shorter hospitalization duration. Doxycycline, however, remains an economical and safe alternative for mild-to-moderate cases. Antibiotic selection should be guided by local resistance data, patient comorbidities, and cost considerations.

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