Roberta Pisi

Purpose: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder that generally predisposes to pulmonary emphysema with or without chronic obstructive pulmonary disease (COPD). Despite the lack of spirometric obstruction, early Small Airways Dysfunction (SAD) may occur in AATD patients preceding lung damage. Methods: We conducted a retrospective, single-center study on 60 AATD patients without airflow obstruction (FEV₁/FVC ≥ 0.70). SAD was defined as: reduced spirometric flows (≥2 of FEF25–75, FEF50, FEF75 <65% predicted) and/or IOS R5–R20 value greater than 0.07 kPa•s•L⁻¹. Correlation and agreement between spirometry and IOS were assessed, as well as associations with Modified Medical Research Council (mMRC) dyspnea scores. Results: SAD was detected in 23% of patients by spirometry, 10% by IOS, and 13% by both methods. A slight agreement was found between spirometric and IOS criteria (κ = 0.22). Only IOS-defined SAD was significantly associated with dyspnea (mMRC ≥2; p = 0.05), and R5–R20 values correlated with mMRC scores (r = 0.38, p = 0.003). No association was observed between spirometry-defined SAD and symptoms. Conclusions: These findings support IOS as a partially complementary tool for the early detection of peripheral airway impairment in AATD. Moreover, IOS but not spirometry criteria were related to breathlessness perception in AATD patients without airflow obstruction, with IOS proving to be a clinically more sensitive measure.

Background and Objectives: In adults, 150 to 300 min a week of moderate-intensity physical activity is the recommended daily level to maintain or improve fitness. In subjects with chronic obstructive pulmonary disease (COPD), reductions in daily physical activity (DPA) amounts are related to clinically significant outcomes. In this study, we ascertain whether or not COPD patients, when clustered into active (DPA ≥ 30 min a day, 5 days a week) and inactive (DPA < 30 min a day, 5 days a week), may differ in exercise capacity, as assessed by a cardiopulmonary exercise test (CPET). Materials and Methods: A large sample of clinically stable COPD patients was retrospectively recruited and then underwent spirometry and an incremental ramp protocol 5–15 watts/min CPET. DPA was assessed by a questionnaire. Results: A total of 83 (female 25%, age range 41–85 y) active and 131 (female 31%, age range 49–83 y) inactive participants were enrolled. They were similar in age, sex distribution, body mass index (BMI) and in spirometry. The two groups were significantly different in dyspnea on exertion, as assessed by the modified Medical Research Council (mMRC), and in cardio-metabolic parameters, but not in ventilatory ones, as confirmed by the CPET. Conclusions: COPD patients experiencing physical activity of at least 30 min a day, 5 days a week, showed a greater exercise capacity and an improved cardiovascular response to exercise, when compared to inactive ones. Active and inactive participants did not differ in terms of airflow obstruction severity as well as in dynamic hyperinflation and ventilatory inefficiency during exercise. This study further suggests the benefits of regular physical activity in COPD.

Background: Long-term sequelae, called Long-COVID (LC), may occur after SARS-CoV-2 infection, with unexplained dyspnoea as the most common symptom. The breathing pattern (BP) analysis, by means of the ratio of the inspiratory time (T_I) during the tidal volume (V_T) to the total breath duration (T_I/T_TOT) and by the V_T/T_I ratio, could further elucidate the underlying mechanisms of the unexplained dyspnoea in LC patients. Therefore, we analysed T_I/T_TOT and V_T/T_I at rest and during maximal exercise in LC patients with unexplained dyspnoea, compared to a control group. Methods: In this cross-sectional study, we enrolled LC patients with normal spirometry, who were required to perform a cardio-pulmonary exercise test (CPET) for unexplained dyspnoea, lasting at least 3 months after SARS-CoV-2 infection. As a control group, we recruited healthy age and sex-matched subjects (HS). All subjects performed spirometry and CPET, according to standardized procedures. Results: We found that 42 LC patients (23 females) had lower maximal exercise capacity, both in terms of maximal O₂ uptake (VO₂peak) and workload, compared to 40 HS (22 females) (p < 0.05). LC patients also showed significantly higher values of T_I/T_TOT at rest and at peak, and lower values in V_T/T_I at peak (p < 0.05). In LC patients, values of T_I/T_TOT at peak were significantly related to ∆PETCO₂, i.e., the end-tidal pressure of CO₂ at peak minus the one at rest (p < 0.05). When LC patients were categorized by the T_I/T_TOT 0.38 cut-off value, patients with T_I/T_TOT > 0.38 showed lower values in VO₂peak and maximal workload, and greater values in the ventilation/CO₂ linear relationship slope than patients with T_I/T_TOT ≤ 0.38 (p < 0.05). Conclusions: Our findings show that LC patients with unexplained dyspnoea have resting and exertional BP more prone to diaphragmatic fatigue, and less effective than controls. Pulmonary rehabilitation might be useful to revert this unpleasant condition.

Purpose: Smoking-induced bronchiolitis with progressive small airway dysfunction (SAD) is a leading cause of chronic obstructive pulmonary disease. We investigated the value of using the impulse oscillometry system (IOS) to detect SAD in asymptomatic smokers with preserved spirometry. Patients and Methods: We included 75 asymptomatic smokers (37 females, mean age 47± 12 years, 26± 17 pack/year) with preserved spirometry [forced expiratory volume at 1st second (FEV1)/forced vital capacity (FVC) ≥ 0.70 and normal FVC] and 34 never-smokers (19 females, mean age 42± 15 years). Results: In smokers, pack/years were significantly related to spirometry and IOS parameters (p < 0.05). The values of the fall in resistance from 5 Hz to 20 Hz (R5 – R20) were significantly and inversely related to the values of the ratio of forced expiratory volume in 3 and in 6 seconds (FEV₃/FEV₆) (p < 0.05). In addition, the percentage of heavy smokers (≥ 30 pack/year) with R5 – R20 > 0.07 kPa·s·L^{− 1}, considered as IOS index of SAD, but not with FEV3/FEV6 less than a lower limit of normal, a spirometry index of SAD, was significantly higher than that of mild smokers (< 30 pack/year) and never-smokers (p < 0.05). Conclusion: This study demonstrates that IOS has the potential to detect SAD in asymptomatic heavy smokers with preserved spirometry and with FEV3/FEV6 values in the normal range. We confirm that IOS provides parameters which can complement traditional measurements of pulmonary function.

Although the etiology and disease mechanisms of asthma and alpha-1 antitrypsin deficiency (AATD) are distinct, several reports indicate that asthma is common in AATD patients, however the relations...

We investigated whether a relationship between small airways dysfunction and bronchial hyperresponsiveness (BHR), expressed both in terms of ease of airway narrowing and of excessive bronchoconstriction, could be demonstrated in asthma. 63 (36 F; mean age 42 yr ± 14) stable, mild-to-moderate asthmatic patients (FEV1 92% pred ±14; FEV1/FVC 75% ± 8) underwent the methacholine challenge test (MCT). The degree of BHR was expressed as PD20 (in μg) and as ∆FVC%. Peripheral airway resistance was measured pre- and post-MCT by impulse oscillometry system (IOS) and expressed as R5-R20 (in kPa sL−1). All patients showed BHR to methacholine (PD20 < 1600 μg) with a PD20 geometric (95% CI) mean value of 181(132–249) μg and a ∆FVC% mean value of 13.6% ± 5.1, ranging 2.5 to 29.5%. 30 out of 63 patients had R5-R20 > 0.03 kPa sL−1 (>upper normal limit) and showed ∆FVC%, but not PD20 values significantly different from the 33 patients who had R5-R20 ≤ 0.03 kPa sL−1 (15.8% ± 4.6 vs 11.5% ± 4.8, p < 0.01 and 156(96–254) μg vs 207 (134–322) μg, p = 0.382). In addition, ∆FVC% values were significantly related to the corresponding pre- (r = 0.451, p < 0.001) and post-MCT (r = 0.376, p < 0.01) R5-R20 values. Our results show that in asthmatic patients, small airway dysfunction, as assessed by IOS, is strictly associated to BHR, expressed as excessive bronchoconstriction, but not as ease of airway narrowing.

Background: The role of an elevated body mass index (BMI) in asthma remains controversial. Objectives: To investigate the relationship between overweight (BMI >25 and ≤30), lung function, disease control, and airway inflammation in an asthmatic population. Methods: We consecutively studied 348 patients (age 43 ± 16 years; 211 females). In all patients, BMI, spirometry, the Asthma Control Test (ACT), and fractional exhaled nitric oxide (FeNO; ppb) were measured. Results: One hundred forty-five patients were overweight and, as compared to those with normal BMI, had lower values of FVC, FEV1, and FEV1/FVC and of FEF25–75 even when normalized for FVC (p < 0.05 for each comparison). The ratio between the number of patients with well-controlled asthma (ACT ≥20) and that of patients with poorly controlled asthma (ACT < 20) was significantly lower in overweight patients (1.07 vs. 1.84; χ2 = 6.030, p < 0.01). In overweight patients, the odds ratio of uncontrolled asthma expressed by logistic regression analysis was 1.632 (95% CI = 1.043–2.553), independently of gender, atopy, smoking habit, and inhaled steroid therapy. No difference was observed in FeNO values between overweight and normal weight patients (27.7 ± 2.3 vs. 27.9 ± 2.2 ppb). Conclusions: Our results show that, in an asthmatic population, overweight is associated with airflow obstruction and poor disease control but not with FeNO change. The findings of the present study support the view that other factors besides airway inflammation alone may explain the relationship between asthma and an elevated BMI.