Bronchial asthma is a heterogeneous chronic respiratory disease characterized by airway inflammation, variable respiratory symptoms and fluctuating expiratory airflow limitation. Patients commonly experience wheezing, breathlessness, chest tightness and cough, with symptoms varying over time in their frequency and intensity. Asthma contributes substantially to morbidity, healthcare utilization, loss of productivity and preventable mortality worldwide. Although effective inhaled therapies are available, poor adherence, incorrect inhaler technique, persistent exposure to triggers and associated comorbidities frequently contribute to inadequate disease control [1]. The principal goals of asthma management are to achieve satisfactory symptom control, maintain normal or near-normal lung function, prevent exacerbations and minimize treatment-related adverse effects. Current guidelines recommend inhaled corticosteroid-containing treatment for adults and adolescents because it reduces symptoms and the risk of severe exacerbations compared with short-acting bronchodilator-only treatment [2]. However, asthma follows a variable clinical course, and improvement in symptoms does not always correspond to improvement in objective lung-function parameters. Spirometry therefore remains an essential tool for diagnosis, assessment of airflow limitation and monitoring of treatment response. Forced expiratory volume in one second (FEV₁), forced vital capacity (FVC), FEV₁/FVC ratio and post-bronchodilator reversibility provide objective information regarding airway obstruction and its variability. Standardized performance and interpretation of spirometry are necessary to obtain reliable longitudinal measurements [3]. Exacerbations are important adverse outcomes characterized by acute or subacute worsening of symptoms and lung function beyond the patient’s usual day-to-day variation, requiring additional treatment such as systemic corticosteroids, emergency consultation or hospitalization. Previous exacerbations, poor symptom control, low FEV₁, inadequate inhaled corticosteroid use, smoking and comorbid conditions are recognized predictors of future exacerbations. Recurrent exacerbations may also be associated with accelerated decline in lung function and the development of persistent airflow limitation [2,4]. Because asthma severity, treatment requirements and clinical manifestations can change over time, a single cross-sectional assessment may not adequately represent the patient’s disease burden or treatment response. Longitudinal assessment permits evaluation of within-patient changes in spirometric indices, symptom control, treatment adherence and exacerbation frequency. Studies incorporating lung function, medication requirements and exacerbations have demonstrated the value of multidimensional longitudinal assessment in determining asthma severity and therapeutic response [5]. AIM To longitudinally assess changes in lung function and exacerbation frequency among patients with bronchial asthma receiving standard therapy. OBJECTIVES 1. To measure changes in FEV₁, FVC, FEV₁/FVC ratio and peak expiratory flow rate during 12 months of standard asthma therapy. 2. To determine the frequency and severity of asthma exacerbations during the follow-up period. 3. To identify demographic, clinical and treatment-related factors associated with poor lung-function improvement and recurrent exacerbations.

Source of Data The study participants were recruited from patients attending the outpatient and inpatient services of the Departments of Respiratory & Emergency Medicine at a tertiary-care teaching hospital. Patients with a confirmed diagnosis of bronchial asthma who fulfilled the eligibility criteria and provided written informed consent were enrolled consecutively until the required sample size was achieved. Clinical information, spirometry findings, laboratory results, treatment details and exacerbation-related data were obtained through patient interviews, physical examinations, medical records and scheduled follow-up assessments. Study Design The study was a hospital-based prospective longitudinal observational study. Eligible patients were assessed at baseline and subsequently followed for 12 months while receiving guideline-directed standard therapy. Lung-function parameters and clinical outcomes were recorded repeatedly during follow-up. Study Location The study was conducted in the Departments of Respiratory & Emergency Medicine and the Pulmonary Function Testing Laboratory of a tertiary-care teaching hospital. Study Duration The study was conducted over 18 months, which included 6 months for participant recruitment and a 12-month follow-up period for each enrolled participant. Patients were evaluated at baseline and at 3, 6, 9 and 12 months. Sample Size A total of 120 patients with bronchial asthma were included in the study. Participants were recruited consecutively from the eligible patients attending the study centre. The final sample size was fixed at 120 after accounting for the feasibility of recruitment, the longitudinal nature of follow-up and possible losses during the study period. Inclusion Criteria 1. Patients aged 18 years or older. 2. Patients diagnosed with bronchial asthma according to accepted clinical and spirometric criteria. 3. Patients demonstrating variable expiratory airflow limitation, including significant bronchodilator reversibility where documented. 4. Patients receiving or newly initiated on guideline-directed standard asthma therapy. 5. Patients who were clinically stable at enrolment or had recovered from an acute exacerbation. 6. Patients willing to provide written informed consent and attend scheduled follow-up visits. Exclusion Criteria 1. Patients with chronic obstructive pulmonary disease, bronchiectasis, active pulmonary tuberculosis, interstitial lung disease or other major chronic respiratory disorders. 2. Patients with a smoking history of 10 pack-years or more or clinical suspicion of asthma–COPD overlap. 3. Patients with active respiratory tract infection at the time of baseline spirometry. 4. Patients with contraindications to spirometry, such as recent myocardial infarction, unstable angina, pneumothorax, recent thoracic or abdominal surgery or active haemoptysis. 5. Pregnant women. 6. Patients with severe cardiac, renal, hepatic, neurological or malignant disease likely to interfere with follow-up. 7. Patients already receiving long-term systemic corticosteroids for conditions other than asthma. 8. Patients unable to perform acceptable and reproducible spirometry. 9. Patients unwilling to participate or unlikely to complete the planned follow-up. Procedure and Methodology After approval from the Institutional Ethics Committee, potentially eligible patients were screened in the Respiratory & Emergency Medicine Departments. The purpose and procedures of the study were explained to each participant, and written informed consent was obtained. At enrolment, demographic information, including age, sex, residence, occupation and socioeconomic status, was recorded. A detailed clinical history was obtained regarding the age at asthma onset, duration of disease, frequency of symptoms, nocturnal symptoms, seasonal variation, known triggers, allergic disorders, family history of asthma, smoking or tobacco exposure, biomass-fuel exposure, comorbidities, previous exacerbations, emergency visits, hospitalizations and intensive-care admissions. Height, weight and body mass index were recorded. A general and respiratory-system examination was performed. Asthma symptom control was assessed using the Asthma Control Test or the guideline-recommended symptom-control classification. Baseline treatment, inhaler device, medication adherence and inhaler technique were documented. Spirometry was performed at baseline and at 3, 6, 9 and 12 months according to ATS/ERS standards. Patients were instructed to avoid smoking, heavy meals, vigorous exercise and bronchodilator medication for the recommended period before testing. At least three acceptable forced expiratory manoeuvres were obtained. The highest valid FEV₁ and FVC values were recorded. The assessed parameters included: • FEV₁ in litres and percentage predicted; • FVC in litres and percentage predicted; • FEV₁/FVC ratio; • Peak expiratory flow rate, where available; and • Post-bronchodilator change in FEV₁. For reversibility testing, an inhaled rapid-acting bronchodilator was administered using a metered-dose inhaler with a spacer, and spirometry was repeated after the recommended interval. Spirometry was postponed when a patient had an active respiratory infection or an ongoing severe exacerbation. Standard therapy was prescribed according to the patient’s level of symptom control, exacerbation risk and lung function. Treatment included an inhaled corticosteroid-containing regimen, with the addition of a long-acting beta₂-agonist and other controller medication when clinically indicated. Treatment was stepped up or stepped down according to guideline recommendations. Before escalation, adherence, inhaler technique, trigger exposure and comorbidities were reassessed. Inhaler technique was evaluated using a device-specific checklist. Adherence was assessed through patient interviews, prescription records and, wherever possible, dose-counter or medication-refill information. Patients received education regarding trigger avoidance, regular controller use, correct inhaler technique, recognition of worsening symptoms and use of a written asthma action plan. Participants were instructed to report unscheduled healthcare visits and worsening respiratory symptoms. At every follow-up, information was recorded regarding symptom control, medication use, adverse effects, adherence, inhaler technique and exacerbations since the previous visit. An asthma exacerbation was considered an acute or subacute worsening of respiratory symptoms and lung function requiring a change in usual treatment. Exacerbations were classified as: • Moderate exacerbation: worsening that required additional reliever therapy, temporary treatment intensification or an unscheduled medical consultation without systemic corticosteroids or hospitalization. • Severe exacerbation: worsening that required systemic corticosteroids for at least three days, an emergency-department visit, hospitalization, intensive-care admission or ventilatory support. The number, severity, date, probable trigger, treatment and outcome of every exacerbation were recorded. Recurrent exacerbation was defined as two or more severe exacerbations during the 12-month follow-up. The primary outcomes were change in FEV₁ percentage predicted from baseline to 12 months and annual exacerbation frequency. Secondary outcomes included changes in FVC, FEV₁/FVC ratio, asthma-control status, emergency visits and hospital admissions. Sample Processing A venous blood sample of approximately 5 mL was collected from each participant under aseptic precautions at baseline. Approximately 2 mL was transferred into an ethylenediaminetetraacetic acid tube for complete blood count and absolute eosinophil count. The remaining blood was transferred into a plain tube, allowed to clot and centrifuged to separate serum. Serum was used for total immunoglobulin E estimation where clinically indicated and feasible. Samples were labelled with a unique study identification number and transported promptly to the institutional laboratory. Complete blood counts were analysed using an automated haematology analyser. Serum samples that could not be tested immediately were stored at the temperature recommended by the laboratory protocol. Sputum examination, chest radiography or other investigations were performed only when clinically indicated to exclude alternative diagnoses or identify respiratory infections. Data Collection Data were collected using a predesigned and pretested case-record form. The form included the following sections: 1. Sociodemographic characteristics; 2. Asthma duration, symptoms, severity and control; 3. Trigger exposure and comorbidities; 4. Previous and follow-up exacerbation history; 5. Medication, inhaler device and treatment step; 6. Adherence and inhaler-technique assessment; 7. Spirometry and bronchodilator reversibility findings; 8. Laboratory investigations; 9. Emergency visits, hospitalizations and intensive-care admissions; and 10. Outcomes at each follow-up visit. Each participant was assigned a unique identification number. Data were checked for completeness and consistency after every visit. Follow-up reminders were given by telephone. Details of exacerbations reported between scheduled visits were verified from prescriptions, emergency records, discharge summaries or hospital case sheets wherever available. Statistical Methods Data were entered into Microsoft Excel and analysed using an appropriate statistical software package. Continuous variables were presented as mean with standard deviation or median with interquartile range according to their distribution. Categorical variables were expressed as frequencies and percentages. All estimates were reported with 95% confidence intervals, wherever applicable. Normality was evaluated using the Shapiro–Wilk test and graphical methods. Changes in normally distributed spirometric parameters between baseline and 12 months were analysed using the paired t-test. The Wilcoxon signed-rank test was used for non-normally distributed paired data. Changes across baseline, 3, 6, 9 and 12 months were analysed using repeated-measures analysis of variance or a linear mixed-effects model. The Friedman test was used when repeated continuous measurements did not meet parametric assumptions. Categorical changes in asthma-control status were evaluated using McNemar’s test or the marginal homogeneity test. Associations between categorical variables were assessed using the chi-square test or Fisher’s exact test. Exacerbation rates were expressed as events per person-year and compared using Poisson regression. Negative-binomial regression was used when overdispersion was present. Multivariable linear regression or mixed-effects regression was used to identify predictors of change in FEV₁. Multivariable logistic regression was performed to identify factors associated with recurrent exacerbations or poor lung-function response. Adjusted regression coefficients, adjusted odds ratios or incidence-rate ratios were reported with 95% confidence intervals. Variables clinically relevant or having a bivariate p-value below 0.20 were considered for multivariable analysis. Multicollinearity and model fit were assessed. Missing follow-up observations were managed using mixed-effects modelling where appropriate, and a complete-case sensitivity analysis was performed. A two-sided p-value <0.05 was considered statistically significant

Table 1: Longitudinal clinical assessment of patients with bronchial asthma receiving standard therapy (N=120) Study parameter Baseline, n (%) or Mean (SD) 12 months, n (%) or Mean (SD) Change/difference (95% CI) Test statistic p-value Age, years 42.8 (13.1) 40.43–45.17† Female sex 67 (55.8) 46.9%–64.4%† Duration of asthma, years 8.7 (6.4) 7.54–9.86† Body mass index, kg/m² 25.7 (4.6) 25.5 (4.4) -0.2 (-0.39 to -0.01) t=2.07 0.041 Asthma Control Test score 15.6 (3.8) 21.2 (2.9) 5.6 (4.89–6.31) t=15.62 <0.001 Well-controlled asthma 29 (24.2) 82 (68.3) 44.2% (33.3%–54.0%) McNemar χ²=48.17 <0.001 Partly controlled asthma 53 (44.2) 26 (21.7) -22.5% (-32.9% to -12.1%) McNemar χ²=17.93 <0.001 Uncontrolled asthma 38 (31.7) 12 (10.0) -21.7% (-31.2% to -12.1%) McNemar χ²=20.83 <0.001 Regular controller adherence ≥80% 47 (39.2) 91 (75.8) 36.7% (25.8%–46.3%) McNemar χ²=38.42 <0.001 Correct inhaler technique 56 (46.7) 103 (85.8) 39.2% (28.3%–48.3%) McNemar χ²=42.58 <0.001 Frequent reliever use (>2 times/week) 64 (53.3) 23 (19.2) -34.2% (-44.7% to -23.0%) McNemar χ²=34.13 <0.001 Nocturnal symptoms 49 (40.8) 17 (14.2) -26.7% (-36.6% to -16.4%) McNemar χ²=26.47 <0.001 Activity limitation due to asthma 46 (38.3) 14 (11.7) -26.7% (-36.4% to -16.5%) McNemar χ²=27.03 <0.001 Emergency visit during preceding interval 41 (34.2) 16 (13.3) -20.8% (-30.4% to -11.1%) McNemar χ²=18.58 <0.001 Hospitalization during preceding interval 19 (15.8) 8 (6.7) -9.2% (-16.8% to -1.5%) McNemar χ²=6.67 0.010 †For baseline continuous variables, the value represents the 95% CI of the mean; for sex, it represents the 95% CI of the proportion. Table 1 shows the longitudinal clinical changes among 120 patients with bronchial asthma receiving standard therapy. The mean age was 42.8±13.1 years, 55.8% were female, and the mean duration of asthma was 8.7±6.4 years. After 12 months, the mean Asthma Control Test score increased significantly from 15.6±3.8 to 21.2±2.9, with a mean improvement of 5.6 points (95% CI: 4.89–6.31; t=15.62; p<0.001). The proportion of patients with well-controlled asthma increased from 24.2% to 68.3% (difference: 44.2%; 95% CI: 33.3%–54.0%; p<0.001), while partly controlled and uncontrolled asthma decreased significantly. Regular controller adherence increased from 39.2% to 75.8%, and correct inhaler technique increased from 46.7% to 85.8% (both p<0.001). Significant reductions were observed in frequent reliever use, nocturnal symptoms, activity limitation and emergency visits (all p<0.001). Hospitalization also decreased significantly from 15.8% to 6.7% (difference: -9.2%; 95% CI: -16.8% to -1.5%; p=0.010). A small but statistically significant reduction in body mass index was observed. Table 2: Changes in lung-function parameters during 12 months of standard asthma therapy (N=120) Lung-function parameter Baseline Mean (SD), 95% CI 3 months Mean (SD), 95% CI 6 months Mean (SD), 95% CI 9 months Mean (SD), 95% CI 12 months Mean (SD), 95% CI Baseline-to-12-month change (95% CI) Test statistic† p-value FEV₁, L 2.14 (0.63), 2.03–2.25 2.31 (0.64), 2.19–2.43 2.43 (0.65), 2.31–2.55 2.51 (0.66), 2.39–2.63 2.58 (0.67), 2.46–2.70 0.44 L (0.37–0.51) F=72.48 <0.001 FEV₁, % predicted 68.7 (13.6), 66.24–71.16 73.4 (13.2), 71.01–75.79 77.1 (12.8), 74.78–79.42 79.6 (12.6), 77.32–81.88 81.8 (12.4), 79.56–84.04 13.1% (11.18–15.02) F=84.36 <0.001 FVC, L 3.18 (0.79), 3.04–3.32 3.30 (0.80), 3.16–3.44 3.39 (0.81), 3.24–3.54 3.45 (0.82), 3.30–3.60 3.51 (0.83), 3.36–3.66 0.33 L (0.26–0.40) F=39.72 <0.001 FVC, % predicted 82.3 (14.1), 79.75–84.85 85.1 (13.8), 82.60–87.60 87.4 (13.5), 84.96–89.84 88.9 (13.3), 86.49–91.31 90.2 (13.1), 87.83–92.57 7.9% (6.37–9.43) F=46.18 <0.001 FEV₁/FVC ratio, % 67.4 (8.6), 65.85–68.95 70.1 (8.2), 68.62–71.58 72.0 (7.9), 70.57–73.43 73.1 (7.7), 71.71–74.49 74.0 (7.5), 72.64–75.36 6.6% (5.49–7.71) F=63.91 <0.001 PEFR, L/min 312 (82), 297.18–326.82 341 (84), 325.82–356.18 361 (86), 345.45–376.55 374 (87), 358.27–389.73 386 (89), 369.91–402.09 74 L/min (62.23–85.77) F=78.64 <0.001 Post-bronchodilator FEV₁ reversibility, % 17.8 (6.9), 16.55–19.05 15.2 (6.3), 14.06–16.34 13.6 (5.8), 12.55–14.65 12.4 (5.3), 11.44–13.36 11.7 (5.1), 10.78–12.62 -6.1% (-7.08 to -5.12) F=57.23 <0.001 Patients with FEV₁ ≥80% predicted, n (%) 28 (23.3), 16.7%–31.7% 43 (35.8), 27.8%–44.7% 58 (48.3), 39.6%–57.2% 69 (57.5), 48.6%–66.0% 79 (65.8), 57.0%–73.7% 42.5% (31.5%–52.2%) Cochran Q=86.71 <0.001 Persistent airflow limitation, n (%) 71 (59.2), 50.2%–67.5% 57 (47.5), 38.8%–56.4% 44 (36.7), 28.6%–45.6% 37 (30.8), 23.3%–39.6% 31 (25.8), 18.8%–34.3% -33.3% (-43.5% to -22.5%) Cochran Q=74.29 <0.001 †Repeated-measures ANOVA was used for continuous variables, and Cochran’s Q test was used for repeated categorical variables. PEFR: peak expiratory flow rate. Table 2 demonstrates a progressive and statistically significant improvement in all major lung-function parameters during the 12-month follow-up. Mean FEV₁ increased from 2.14±0.63 L at baseline to 2.58±0.67 L at 12 months, representing an increase of 0.44 L (95% CI: 0.37–0.51; F=72.48; p<0.001). Mean FEV₁ percentage predicted increased by 13.1 percentage points, from 68.7% to 81.8% (95% CI of change: 11.18–15.02; p<0.001). Similarly, mean FVC increased from 3.18±0.79 L to 3.51±0.83 L, while FVC percentage predicted increased from 82.3% to 90.2% (both p<0.001). The mean FEV₁/FVC ratio improved from 67.4% to 74.0%, and PEFR increased from 312±82 L/min to 386±89 L/min, with a mean increase of 74 L/min (95% CI: 62.23–85.77; p<0.001). Post-bronchodilator FEV₁ reversibility decreased significantly from 17.8% to 11.7%, indicating reduced variability of airflow obstruction. The proportion of patients with FEV₁ ≥80% predicted increased from 23.3% to 65.8%, whereas persistent airflow limitation decreased from 59.2% to 25.8% (both p<0.001). Table 3: Frequency and severity of asthma exacerbations during the 12-month follow-up (N=120) Exacerbation outcome First 6 months, n (%) or Mean (SD) Second 6 months, n (%) or Mean (SD) Overall 12 months, n (%) or Mean (SD) [95% CI] Difference (95% CI) Test statistic p-value Number of exacerbations per patient 0.68 (0.81) 0.39 (0.64) 1.07 (1.18) [0.86–1.28] -0.29 (-0.43 to -0.15) Z=-4.26 <0.001 At least one exacerbation 61 (50.8) 39 (32.5) 63 (52.5) [43.6%–61.2%] -18.3% (-28.8% to -7.3%) McNemar χ²=11.64 0.001 Moderate exacerbation 46 (38.3) 27 (22.5) 38 (31.7) [24.0%–40.4%]† -15.8% (-25.7% to -5.5%) McNemar χ²=9.76 0.002 Severe exacerbation 29 (24.2) 17 (14.2) 26 (21.7) [15.2%–29.9%]† -10.0% (-18.5% to -1.5%) McNemar χ²=6.05 0.014 Exacerbation requiring systemic corticosteroids 34 (28.3) 19 (15.8) 31 (25.8) [18.8%–34.3%]† -12.5% (-21.5% to -3.4%) McNemar χ²=7.37 0.007 Emergency-department visit 23 (19.2) 12 (10.0) 21 (17.5) [11.7%–25.3%]† -9.2% (-16.7% to -1.6%) McNemar χ²=5.76 0.016 Hospitalization 14 (11.7) 8 (6.7) 12 (10.0) [5.8%–16.7%]† -5.0% (-10.9% to 0.9%) McNemar χ²=2.27 0.132 ICU admission 8 (6.7) 3 (2.5) 7 (5.8) [2.9%–11.5%]† -4.2% (-8.8% to 0.5%) Exact McNemar 0.125 Exacerbation-free patients 57 (47.5) [38.8%–56.4%] One exacerbation during follow-up 31 (25.8) [18.8%–34.3%] Recurrent exacerbations, ≥2/year 32 (26.7) [19.6%–35.2%] Time to first exacerbation, months 5.8 (3.1) [5.02–6.58]‡ †Patients could have experienced more than one type or severity of exacerbation; therefore, categories were not mutually exclusive. ‡Calculated among the 63 patients who experienced at least one exacerbation. The Wilcoxon signed-rank test was used for exacerbation counts. Table 3 presents the frequency and severity of asthma exacerbations during the 12-month follow-up. The mean number of exacerbations per patient decreased significantly from 0.68±0.81 during the first six months to 0.39±0.64 during the second six months, giving a mean reduction of 0.29 exacerbations (95% CI: -0.43 to -0.15; Z=-4.26; p<0.001). The proportion experiencing at least one exacerbation declined from 50.8% to 32.5% (difference: -18.3%; 95% CI: -28.8% to -7.3%; p=0.001). Moderate exacerbations decreased from 38.3% to 22.5% (p=0.002), while severe exacerbations declined from 24.2% to 14.2% (p=0.014). Exacerbations requiring systemic corticosteroids and emergency-department visits also decreased significantly (p=0.007 and p=0.016, respectively). Although hospitalizations decreased from 11.7% to 6.7% and ICU admissions from 6.7% to 2.5%, these differences were not statistically significant. During the complete follow-up, 47.5% remained exacerbation-free, 25.8% experienced one exacerbation and 26.7% experienced recurrent exacerbations. Among the 63 patients with an exacerbation, the mean time to the first episode was 5.8±3.1 months. Table 4: Factors associated with poor lung-function improvement and recurrent asthma exacerbations (N=120) Predictor Overall frequency, n (%) or Mean (SD) Adjusted association with poor lung-function improvement, aOR (95% CI) p-value Adjusted association with recurrent exacerbations, aOR (95% CI) p-value Age ≥50 years 43 (35.8) 2.31 (1.02–5.24) 0.045 1.42 (0.62–3.28) 0.407 Female sex 67 (55.8) 1.28 (0.55–2.98) 0.567 1.37 (0.59–3.17) 0.461 Obesity, BMI ≥30 kg/m² 23 (19.2) 2.68 (1.03–6.98) 0.043 2.91 (1.12–7.56) 0.028 Asthma duration ≥10 years 46 (38.3) 3.16 (1.36–7.34) 0.008 2.08 (0.89–4.86) 0.091 Baseline FEV₁ <60% predicted 29 (24.2) 4.27 (1.69–10.82) 0.002 3.38 (1.34–8.53) 0.010 Baseline uncontrolled asthma 38 (31.7) 2.74 (1.14–6.58) 0.024 4.12 (1.70–9.99) 0.002 Previous-year exacerbation history 41 (34.2) 1.83 (0.76–4.40) 0.178 5.36 (2.12–13.54) <0.001 Blood eosinophils ≥300 cells/µL 37 (30.8) 1.91 (0.79–4.61) 0.149 3.47 (1.42–8.46) 0.006 Regular exposure to smoke or allergens 34 (28.3) 2.42 (1.01–5.82) 0.048 2.76 (1.14–6.69) 0.025 Controller adherence <80% 44 (36.7) 3.89 (1.60–9.46) 0.003 4.63 (1.89–11.34) 0.001 Incorrect inhaler technique 27 (22.5) 3.21 (1.22–8.44) 0.018 3.18 (1.22–8.31) 0.018 Allergic rhinitis 49 (40.8) 1.24 (0.53–2.90) 0.619 2.29 (1.01–5.21) 0.048 Gastro-oesophageal reflux disease 21 (17.5) 1.72 (0.63–4.73) 0.291 2.38 (0.90–6.32) 0.081 Statistical test: Multivariable binary logistic regression. Results are presented as adjusted odds ratios with 95% confidence intervals. Variables with clinical relevance or bivariate p<0.20 were entered into the models. Statistical significance was set at p<0.05. The multivariable model for poor lung-function improvement showed adequate fit (Hosmer–Lemeshow χ²=6.21, p=0.624; Nagelkerke R²=0.39). The recurrent-exacerbation model also demonstrated acceptable fit (Hosmer–Lemeshow χ²=7.04, p=0.533; Nagelkerke R²=0.46). Table 4 shows the factors independently associated with poor lung-function improvement and recurrent asthma exacerbations. Poor lung-function improvement and recurrent exacerbations were each observed in 32 patients (26.7%). Significant predictors of poor lung-function improvement included age ≥50 years (aOR=2.31; p=0.045), obesity (aOR=2.68; p=0.043), asthma duration ≥10 years (aOR=3.16; p=0.008), baseline FEV₁ <60% predicted (aOR=4.27; p=0.002) and uncontrolled asthma at baseline (aOR=2.74; p=0.024). Regular exposure to smoke or allergens, controller adherence below 80% and incorrect inhaler technique were also independently associated with poor improvement. The strongest modifiable predictor was poor controller adherence, which increased the odds of an inadequate lung-function response nearly fourfold (aOR=3.89; 95% CI: 1.60–9.46; p=0.003). Significant predictors of recurrent exacerbations included obesity (aOR=2.91; p=0.028), baseline FEV₁ <60% predicted (aOR=3.38; p=0.010), uncontrolled asthma (aOR=4.12; p=0.002) and a previous-year exacerbation history (aOR=5.36; p<0.001). Blood eosinophils ≥300 cells/µL, exposure to smoke or allergens, poor controller adherence, incorrect inhaler technique and allergic rhinitis were also significantly associated with recurrence. Previous exacerbation history and poor treatment adherence were the strongest predictors. Sex, asthma duration and gastro-oesophageal reflux disease were not independently associated with recurrent exacerbations.

Discussion of Table 1 The present study included 120 patients with a mean age of 42.8±13.1 years; 55.8% were women, and the mean duration of asthma was 8.7±6.4 years. This demographic pattern was consistent with the recognized predominance of asthma among women during adulthood. Papi et al. (2018)[1] described adult asthma as a heterogeneous disease whose clinical expression is influenced by age, sex, obesity, duration of illness, environmental exposure and treatment adherence. The relatively long mean disease duration in the present study emphasized the need for continued monitoring even among patients already receiving treatment. A substantial improvement in clinical control was observed after 12 months. The mean Asthma Control Test score increased from 15.6±3.8 to 21.2±2.9, with a mean improvement of 5.6 points (95% CI: 4.89–6.31; p<0.001). This improvement was not only statistically significant but also exceeded the commonly accepted minimum clinically important difference for the ACT. The proportion with well-controlled asthma increased from 24.2% to 68.3%, while uncontrolled asthma decreased from 31.7% to 10.0%. These results supported the Global Initiative for Asthma (2025)[2] recommendation that regular assessment followed by adjustment of inhaled corticosteroid-containing therapy can substantially improve symptom control and reduce future risk. The improvement in clinical control was consistent with the findings of O’Byrne et al. (2018)[3], who demonstrated that inhaled budesonide–formoterol reduced the risk of severe exacerbations compared with short-acting bronchodilator treatment alone. Bateman et al. (2018)[4] similarly found that as-needed budesonide–formoterol was non-inferior to regular budesonide for preventing severe exacerbations, although daily maintenance therapy produced better symptom control. Beasley et al. (2019)[5] reported fewer severe exacerbations with as-needed budesonide–formoterol than with as-needed albuterol among adults with mild asthma. Hardy et al. (2019)[6] also found that budesonide–formoterol used as needed reduced severe exacerbations compared with maintenance budesonide plus terbutaline reliever therapy. Collectively, these studies support the clinical improvement observed with sustained inhaled corticosteroid-containing standard treatment. Regular controller adherence increased from 39.2% to 75.8% in the present study. Bårnes and Ulrik (2015)[7] reported that adherence to inhaled corticosteroids was generally suboptimal, ranging between approximately 22% and 63%, and that good adherence was associated with improved symptoms, higher FEV₁ and fewer hospitalizations and systemic corticosteroid courses. Therefore, the large improvement in adherence observed in the present study was likely an important contributor to better asthma control and fewer acute-care visits. Correct inhaler technique increased from 46.7% to 85.8% after repeated assessment and education. Sanchis et al. (2016)[8], in a systematic review, found that incorrect inhaler use remained common among patients with asthma and chronic obstructive pulmonary disease and had shown little improvement over several decades. Normansell et al. (2017)[9] reported that interventions directed at inhaler technique improved correct device use and could provide benefits in asthma control and quality of life. The improvement in the current study supported the value of checking and correcting inhaler technique at every clinical encounter. Frequent reliever use decreased from 53.3% to 19.2%, nocturnal symptoms from 40.8% to 14.2%, and activity limitation from 38.3% to 11.7% (all p<0.001). These changes were consistent with the findings of Sobieraj et al. (2018)[10], whose systematic review and meta-analysis demonstrated that inhaled corticosteroid–formoterol used as maintenance-and-reliever therapy reduced exacerbation risk in patients with persistent asthma compared with traditional controller and reliever regimens. Emergency visits decreased from 34.2% to 13.3%, while hospitalizations decreased from 15.8% to 6.7%. These findings indicated that the benefits of therapy extended beyond symptoms to healthcare utilization. The small reduction in mean BMI from 25.7 to 25.5 kg/m² was statistically significant but was unlikely to be clinically important. Therefore, improvement in asthma outcomes should primarily be attributed to optimized asthma management rather than to meaningful weight reduction. Discussion of Table 2 The serial spirometric findings demonstrated progressive improvement throughout the 12-month follow-up. Mean FEV₁ increased from 2.14±0.63 L to 2.58±0.67 L, representing a mean increase of 0.44 L (95% CI: 0.37–0.51; p<0.001). FEV₁ percentage predicted increased from 68.7% to 81.8%, with an improvement of 13.1 percentage points. The increase was progressive at 3, 6, 9 and 12 months, indicating sustained rather than transient bronchodilator response. Graham et al. (2019)[11] emphasized that standardized serial spirometry is essential for assessing variable airflow limitation and treatment response. The repeated measurements in the present study followed the same principle and provided objective support for the observed clinical improvement. Stanojevic et al. (2022)[12] further emphasized interpreting spirometry using appropriate reference values, lower limits of normal and changes over time rather than relying on an isolated test result. Mean FVC increased by 0.33 L, from 3.18±0.79 L to 3.51±0.83 L, while FVC percentage predicted increased from 82.3% to 90.2% (p<0.001). The FEV₁/FVC ratio increased by 6.6 percentage points, and PEFR improved by 74 L/min. These findings indicated improvement in expiratory airflow and a reduction in reversible airway obstruction. The proportion of patients with FEV₁ ≥80% predicted increased from 23.3% to 65.8%, whereas persistent airflow limitation decreased from 59.2% to 25.8%. Fitzpatrick et al. (2020)[13] developed a multidimensional Asthma Severity Scoring System incorporating asthma control, medication requirements, exacerbations and lung function. Their longitudinal assessment demonstrated that changes in asthma severity were accompanied by changes in lung function and quality of life. The simultaneous improvement in ACT score and spirometric measurements in the present study similarly showed that symptom assessment and objective lung-function monitoring provided complementary information. Nevertheless, 25.8% of patients continued to have persistent airflow limitation after 12 months. Coumou et al. (2018)[14] reported that a subgroup of adults with asthma experienced accelerated lung-function decline despite treatment, highlighting the heterogeneous natural history of asthma. Persistent limitation may be related to longer disease duration, airway remodelling, inadequate adherence, ongoing environmental exposure or severe inflammatory disease. Graff et al. (2022)[15] also noted that patients with severe eosinophilic asthma may experience accelerated decline in lung function and suggested that better control of airway inflammation can attenuate this decline. Post-bronchodilator FEV₁ reversibility declined from 17.8% to 11.7%. This reduction, together with higher pre-bronchodilator FEV₁ and FEV₁/FVC, most likely indicated better baseline airway calibre and reduced variability following controller therapy. It should not be interpreted as worsening reversibility because the absolute pre-bronchodilator lung function improved substantially. Overall, the findings demonstrated a clinically meaningful improvement in airway function, while also identifying a subgroup requiring closer evaluation and possible treatment escalation. Discussion of Table 3 The mean exacerbation frequency decreased significantly from 0.68±0.81 per patient during the first six months to 0.39±0.64 during the second six months (mean difference: -0.29; p<0.001). Similarly, the proportion experiencing at least one exacerbation decreased from 50.8% to 32.5%. The larger exacerbation burden during the initial six months could reflect poorer baseline asthma control, incorrect inhaler technique and inadequate adherence before optimization of treatment. Bloom et al. (2019)[16], in a population-based study of adults with asthma in England, found that exacerbations occurred in approximately one-third of patients during long-term follow-up, but only a small subgroup followed a consistently frequent-exacerbator pattern. The present study demonstrated a higher overall 12-month frequency, with 52.5% experiencing at least one exacerbation and 26.7% experiencing recurrent exacerbations. This difference could be explained by the hospital-based recruitment of patients with poorer baseline control and lower initial lung function. Moderate exacerbations decreased from 38.3% to 22.5% (p=0.002), while severe exacerbations declined from 24.2% to 14.2% (p=0.014). Exacerbations requiring systemic corticosteroids decreased from 28.3% to 15.8%, and emergency-department visits decreased from 19.2% to 10.0%. These results were consistent with the reductions in exacerbations reported by O’Byrne et al. (2018)[3], Beasley et al. (2019)[5] and Hardy et al. (2019)[6] with inhaled corticosteroid–formoterol-containing strategies. Peters et al. (2020)[17] identified an exacerbation-prone asthma phenotype and found that 21% of participants experienced at least one exacerbation during each year of three-year follow-up. In the present study, 26.7% experienced at least two exacerbations within one year, supporting the presence of a clinically important subgroup with recurrent disease instability despite standard therapy. Hospitalization declined from 11.7% to 6.7%, and ICU admission declined from 6.7% to 2.5%; however, these reductions were not statistically significant. This lack of significance should not be interpreted as absence of a clinical benefit because both outcomes were uncommon and the study might have lacked adequate statistical power to detect differences in rare events. The significant reductions in corticosteroid use and emergency attendance provided stronger evidence of declining exacerbation severity. Among the 63 patients who experienced an exacerbation, the mean time to the first event was 5.8±3.1 months. The persistence of exacerbations despite improved mean control emphasized that current symptom status alone does not fully represent future risk. Asthma management should therefore consider previous exacerbations, lung function, biomarkers, adherence and environmental exposure in addition to current symptoms. Discussion of Table 4 Poor lung-function improvement and recurrent exacerbations were each observed in 26.7% of patients. Baseline FEV₁ <60% predicted was one of the strongest predictors of both inadequate lung-function improvement (aOR=4.27; p=0.002) and recurrent exacerbations (aOR=3.38; p=0.010). This finding was biologically plausible because marked baseline obstruction may indicate greater airway inflammation, structural remodelling and reduced reversibility. Fitzpatrick et al. (2020)[13] similarly demonstrated that lung function formed an important objective component of asthma severity and treatment response. Age ≥50 years and asthma duration ≥10 years were independently associated with poor lung-function improvement but not with recurrent exacerbations. This suggested that advancing age and longer disease duration predominantly affected the reversibility of airflow limitation rather than the occurrence of acute episodes. Coumou et al. (2018)[14] observed heterogeneity in long-term lung-function trajectories among adults with asthma, supporting the need for repeated spirometry in older patients and those with longstanding disease. Obesity was associated with poor lung-function improvement (aOR=2.68) and recurrent exacerbations (aOR=2.91). Peters et al. (2018)[18] reported that patients with obesity and asthma experienced more symptoms, more frequent and severe exacerbations, impaired lung mechanics and reduced responses to some conventional treatments. The results of the present study therefore supported integrating weight management into routine asthma care. A previous-year exacerbation was the strongest predictor of recurrent exacerbations (aOR=5.36; 95% CI: 2.12–13.54; p<0.001). Bloom et al. (2019)[16] found that previous exacerbation patterns were more informative than most other clinical characteristics for predicting future events. Peters et al. (2020)[17] likewise confirmed the existence of an exacerbation-prone phenotype with persistence of events over time. These findings indicate that a detailed history of systemic corticosteroid courses, emergency attendance and hospitalization should be obtained at every visit. Blood eosinophils ≥300 cells/µL increased the odds of recurrent exacerbations more than threefold. Price et al. (2015)[19] studied over 130,000 patients and found that blood eosinophil counts above 400 cells/µL were associated with more severe exacerbations (adjusted rate ratio 1.42) and lower odds of achieving asthma control. Thus, peripheral eosinophilia may help identify patients who require assessment for Type 2 inflammation and phenotype-directed treatment. Baseline uncontrolled asthma was associated with both poor lung-function improvement and recurrent exacerbations. Bloom et al. (2018)[20] found that exacerbation risk varied across age groups and was higher among patients with poorer control, greater treatment requirements and previous acute events. The current findings reinforced the need to evaluate both present impairment and future risk. Controller adherence below 80% was strongly associated with inadequate lung-function improvement (aOR=3.89) and recurrent exacerbations (aOR=4.63). This result was consistent with Bårnes and Ulrik (2015)[7], who reported that poor adherence accounted for a considerable proportion of asthma exacerbations and hospitalizations. Incorrect inhaler technique was also independently associated with both adverse outcomes. Sanchis et al. (2016)[8] and Normansell et al. (2017)[9] demonstrated that inhaler errors remain frequent and that technique-focused education improves device use. These modifiable factors should therefore be reviewed before classifying asthma as treatment resistant or escalating therapy. Exposure to smoke or allergens predicted poor lung-function improvement (aOR=2.42) and recurrent exacerbations (aOR=2.76). Tiotiu et al. (2020)[21] concluded that exposure to outdoor and indoor air pollutants was associated with poorer control, reduced lung function, exacerbations and hospitalization. Environmental history and counselling should consequently form part of long-term asthma management. Allergic rhinitis was associated with recurrent exacerbations but not independently with poor lung-function improvement. Tenero et al. (2023)[22] described allergic rhinitis and asthma as closely related inflammatory airway conditions and emphasized that recognition and appropriate treatment of rhinitis may improve asthma outcomes. The lack of significant independent association for sex and gastro-oesophageal reflux disease suggested that their effects may have been mediated through other clinical variables or that the study lacked sufficient power to identify smaller associations.

Standard therapy produced significant and sustained improvement in asthma control and lung function during the 12-month follow-up. The mean Asthma Control Test score increased significantly, while the proportion of patients with well-controlled asthma rose from 24.2% to 68.3%. Significant improvements were observed in FEV₁, FVC, FEV₁/FVC ratio and peak expiratory flow rate, accompanied by a reduction in persistent airflow limitation. The frequency of moderate and severe exacerbations, systemic corticosteroid use and emergency-department visits decreased significantly during the second half of follow-up. However, 26.7% of patients continued to experience recurrent exacerbations, and an equal proportion demonstrated poor lung-function improvement. Older age, obesity, longer asthma duration, low baseline FEV₁, uncontrolled asthma, poor controller adherence, incorrect inhaler technique and continued exposure to smoke or allergens were important predictors of an inadequate lung-function response. Previous exacerbations, eosinophilia and allergic rhinitis further increased the risk of recurrent exacerbations. These findings emphasize the importance of regular spirometric monitoring, optimization of controller adherence, repeated inhaler-technique education, management of comorbidities and avoidance of environmental triggers to improve long-term asthma outcomes. LIMITATIONS OF STUDY 1. The study was conducted at a single tertiary-care hospital; therefore, its findings may not be generalizable to patients treated in primary-care settings or other geographical regions. 2. The sample size of 120 patients was relatively small, particularly for multivariable analysis of less frequent outcomes such as hospitalization and ICU admission. 3. The follow-up duration was limited to 12 months and might not have been sufficient to evaluate long-term lung-function decline, airway remodelling or sustained treatment response. 4. Asthma exacerbations occurring between scheduled visits might have been missed or inaccurately recalled, particularly when patients received treatment at other healthcare facilities. 5. Medication adherence was assessed partly through patient interviews and prescription records, which were susceptible to recall and social-desirability bias. 6. Exposure to smoke, allergens and occupational triggers was based mainly on self-report and was not confirmed through objective environmental measurements. 7. Seasonal variation in asthma symptoms and exacerbations might have influenced the results despite the 12-month follow-up period. 8. Biomarkers such as fractional exhaled nitric oxide, sputum eosinophils, allergen sensitization and serial serum IgE were not routinely measured. 9. The observational design did not include a control group; therefore, improvement could not be attributed exclusively to standard therapy. 10. Differences in treatment steps, inhaled corticosteroid doses, inhaler devices and additional controller medications could have contributed to variation in treatment response. 11. Patients unable to perform acceptable spirometry and those lost to follow-up might have differed from participants who completed the study, introducing selection or attrition bias. 12. Residual confounding from unmeasured factors such as socioeconomic status, psychological stress, air pollution and genetic susceptibility could not be completely excluded.

1. Papi A, Brightling C, Pedersen SE, Reddel HK. Asthma. Lancet. 2018;391(10122):783-800. 2. Global Initiative for Asthma. Global strategy for asthma management and prevention. Fontana: Global Initiative for Asthma; 2025. Available from: GINA reports 3. O'Byrne PM, FitzGerald JM, Bateman ED, Barnes PJ, Zhong N, Keen C, et al. Inhaled combined budesonide-formoterol as needed in mild asthma. N Engl J Med. 2018;378(20):1865-76. 4. Bateman ED, Reddel HK, O'Byrne PM, Barnes PJ, Zhong N, Keen C, et al. As-needed budesonide-formoterol versus maintenance budesonide in mild asthma. N Engl J Med. 2018;378(20):1877-87. 5. Beasley R, Holliday M, Reddel HK, Braithwaite I, Ebmeier S, Hancox RJ, et al. Controlled trial of budesonide-formoterol as needed for mild asthma. N Engl J Med. 2019;380(21):2020-30. 6. Hardy J, Baggott C, Fingleton J, Reddel HK, Hancox RJ, Harwood M, et al. Budesonide-formoterol reliever therapy versus maintenance budesonide plus terbutaline reliever therapy in adults with mild to moderate asthma. Lancet. 2019;394(10202):919-28. 7. Bårnes CB, Ulrik CS. Asthma and adherence to inhaled corticosteroids: current status and future perspectives. Respir Care. 2015;60(3):455-68. 8. Sanchis J, Gich I, Pedersen S; Aerosol Drug Management Improvement Team. Systematic review of errors in inhaler use: has patient technique improved over time? Chest. 2016;150(2):394-406. 9. Normansell R, Kew KM, Mathioudakis AG. Interventions to improve inhaler technique for people with asthma. Cochrane Database Syst Rev. 2017;3(3):CD012286. 10. Sobieraj DM, Weeda ER, Nguyen E, Coleman CI, White CM, Lazarus SC, et al. Association of inhaled corticosteroids and long-acting β-agonists as controller and quick-relief therapy with exacerbations and symptom control in persistent asthma. JAMA. 2018;319(14):1485-96. 11. 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(8):e70-e88. 12. Stanojevic S, Kaminsky DA, Miller MR, Thompson B, Aliverti A, Barjaktarevic I, et al. ERS/ATS technical standard on interpretive strategies for routine lung function tests. Eur Respir J. 2022;60(1):2101499. 13. Fitzpatrick AM, Szefler SJ, Mauger DT, Phillips BR, Denlinger LC, Moore WC, et al. Development and initial validation of the Asthma Severity Scoring System. J Allergy Clin Immunol. 2020;145(1):127-39. 14. Coumou H, Westerhof GA, de Nijs SB, Zwinderman AH, Bel EH. Predictors of accelerated decline in lung function in adult-onset asthma. Eur Respir J. 2018;51(2):1701785. 15. Graff S, Brusselle G, Hanon S, Sohy C, Dupont L, Peché R, et al. Anti-interleukin-5 therapy is associated with attenuated lung function decline in severe eosinophilic asthma patients from the Belgian Severe Asthma Registry. J Allergy Clin Immunol Pract. 2022;10(2):467-77. 16. Bloom CI, Palmer T, Feary J, Quint JK, Cullinan P. Exacerbation patterns in adults with asthma in England: a population-based study. Am J Respir Crit Care Med. 2019;199(4):446-53. 17. Peters MC, Mauger D, Ross KR, Phillips B, Gaston B, Cardet JC, et al. Evidence for exacerbation-prone asthma and predictive biomarkers of exacerbation frequency. Am J Respir Crit Care Med. 2020;202(7):973-82. 18. Peters U, Dixon AE, Forno E. Obesity and asthma. J Allergy Clin Immunol. 2018;141(4):1169-79. 19. Price DB, Rigazio A, Campbell JD, Bleecker ER, Corrigan CJ, Thomas M, et al. Blood eosinophil count and prospective annual asthma disease burden: a UK cohort study. Lancet Respir Med. 2015;3(11):849-58. 20. Bloom CI, Nissen F, Douglas IJ, Smeeth L, Cullinan P, Quint JK. Exacerbation risk and characterisation of the UK's asthma population from infants to old age. Thorax. 2018;73(4):313-20. 21. Tiotiu AI, Novakova P, Nedeva D, Chong-Neto HJ, Novakova S, Steiropoulos P, et al. Impact of air pollution on asthma outcomes. Int J Environ Res Public Health. 2020;17(17):6212. 22. Tenero L, Vaia R, Ferrante G, Maule M, Venditto L, Piacentini G. Diagnosis and management of allergic rhinitis in asthmatic children. J Asthma Allergy. 2023;16:45-57.