Chronotropic incompetence (CI; failure to reach the targeted heart rate (HR) on exercise) and a delayed HR recovery (HRR; 12 beats decline within the first minute after cessation) reflect autonomic dysfunction (AD) and predict adverse cardiac prognosis. As chronic obstructive pulmonary disease (COPD) is known to be associated with AD, we hypothesized that these patients may manifest these responses on exercise. The prevalence and predictors of these responses in COPD and their association with its severity have not been evaluated. Normoxemic, stable male patients with COPD (n ¼ 39) and 11 healthy controls underwent lung function testing and incremental leg ergometry. HR responses were monitored during exercise and recovery to compute the HRR and CI. Of all the patients, 33 (84.6%) had at least one of the two exercise responses as abnormal, with the majority (23, 58.9%) having both an abnormal HRR and CI. The frequency of abnormal responses increased with increasing Global Initiative for Chronic Obstructive Lung Disease stage and body mass index, airflow obstruction, dyspnoea and exercise capacity index. After adjusting for smoking history and post-bronchodilator forced expiratory volume in 1 second, only a reduced diffusion capacity for carbon monoxide predicted abnormal HRR, though weakly. We concluded that abnormal HRR and CI are common in patients with COPD. These responses are observed with increasing frequency as the severity of disease increases.
Cardiac autonomic dysfunction is an independent determinant of adverse outcomes in many diseases. The available literature on the relative changes in sympathetic and parasympathetic components in chronic obstructive pulmonary disease (COPD) is equivocal, the clinical and physiological correlates are poorly defined and association with markers of systemic inflammation has not been explored. As both autonomic dysfunction and systemic inflammation may contribute to cardiovascular morbidity in COPD, we hypothesized that these may be associated. Sixty three stable patients of COPD and 36 controls underwent spirometry, estimation of diffusion capacity, six-minute walk test and measurements of serum interleukin-6 (IL-6) and high-sensitivity C-Reactive protein. Cardiac autonomic activity was evaluated by standard five-minute heart rate variability (HRV) recordings to obtain time- and frequency-domain indices and the averaged heart rate. We observed that HRV indices of overall autonomic modulation, the standard deviation of time intervals between consecutive normal beats (SDNN) and total power, were greater in patients with higher levels of indices of both parasympathetic and sympathetic activity. The heart rate was significantly higher in patients indicating an overall sympathetic dominance and was inversely correlated with diffusion capacity. Serum IL-6 was inversely correlated with pNN50, an index of parasympathetic activity, and positively with LF/HF ratio, a measure of sympathetic: parasympathetic balance. None of the HRV indices was significantly correlated with physiological measures of severity. It was concluded that patients with COPD have increased cardiac autonomic modulation with sympathetic dominance. This is associated with decreased lung diffusion capacity and systemic inflammation.
Background COVID‐19‐associated pulmonary aspergillosis (CAPA) has been widely reported but homogenous large cohort studies are needed to gain real‐world insights about the disease. Methods We collected clinical and laboratory data of 1161 patients hospitalised at our Institute from March 2020 to August 2021, defined their CAPA pathology, and analysed the data of CAPA/non‐CAPA and deceased/survived CAPA patients using univariable and multivariable models. Results The overall prevalence and mortality of CAPA in our homogenous cohort of 1161 patients were 6.4% and 47.3%, respectively. The mortality of CAPA was higher than that of non‐CAPA patients (hazard ratio: 1.8 [95% confidence interval: 1.1–2.8]). Diabetes (odds ratio [OR] 1.92 [1.15–3.21]); persistent fever (2.54 [1.17–5.53]); hemoptysis (7.91 [4.45–14.06]); and lung lesions of cavitation (8.78 [2.27–34.03]), consolidation (9.06 [2.03–40.39]), and nodules (8.26 [2.39–28.58]) were associated with development of CAPA by multivariable analysis. Acute respiratory distress syndrome (ARDS) (2.68 [1.09–6.55]), a high computed tomography score index (OR 1.18 [1.08–1.29]; p < .001), and pulse glucocorticoid treatment (HR 4.0 [1.3–9.2]) were associated with mortality of the disease. Whereas neutrophilic leukocytosis (development: 1.09 [1.03–1.15] and mortality: 1.17 [1.08–1.28]) and lymphopenia (development: 0.68 [0.51–0.91] and mortality: 0.40 [0.20–0.83]) were associated with the development as well as mortality of CAPA. Conclusion We observed a low but likely underestimated prevalence of CAPA in our study. CAPA is a disease with high mortality and diabetes is a significant factor for its development while ARDS and pulse glucocorticoid treatment are significant factors for its mortality. Cellular immune dysregulation may have a central role in CAPA from its development to mortality.
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