Small airways in asthma: From inflammation and pathophysiology to treatment response.

Small airways are characterized as those with an inner diameter less than 2 mm and constitute a major site of pathology and inflammation in asthma disease. It is estimated that small airways dysfunction may occur before the emergence of noticeable symptoms, spirometric abnormalities and imaging findings, thus characterizing them as "the quiet or silent zone" of the lungs. Despite their importance, measuring and quantifying small airways dysfunction presents a considerable challenge due to their inaccessibility in usual functional measurements, primarily due to their size and peripheral localization. Several pulmonary function tests have been proposed for the assessment of the small airways, including impulse oscillometry, nitrogen washout, body plethysmography, as well as imaging methods. Nevertheless, none of these methods has been established as the definitive "gold standard," thus, a combination of them should be used for an effective assessment of the small airways. Widely used asthma treatments seem to also affect several parameters of the small airways. Emerging biologic treatments show promising results in reducing small airways inflammation and remodelling, providing evidence for potential alterations in the disease's progression and outcomes. These novel therapies have implications not only in the clinical aspects of asthma but also in its inflammatory and functional aspects.

Small Airways Dysfunction and Lung Hyperinflation in Long COVID-19 Patients as Potential Mechanisms of Persistent Dyspnoea.

BACKGROUND: Reticulation, ground glass opacities and post-infection bronchiectasis are present three months following hospitalisation in patients recovering from SARS-CoV-2 infection and are associated with the severity of acute infection. However, scarce data exist on small airways impairment and lung hyperinflation in patients with long COVID-19. AIM: To evaluate small airways function and lung hyperinflation in previously hospitalised patients with long COVID-19 and their association with post-COVID-19 breathlessness. METHODS: In total, 33 patients (mean ± SD, 53 ± 11 years) with long COVID-19 were recruited 149 ± 90 days following hospital discharge. Pulmonary function tests were performed and lung hyperinflation was defined as RV/TLC ≥ 40%. Small airways function was evaluated by measuring the closing volume (CV) and closing capacity (CC) using the single-breath nitrogen washout technique (SBN2W). RESULTS: CC was 115 ± 28% pred. and open capacity (OC) was 90 ± 19. CC was abnormal in 13 patients (39%), CV in 2 patients (6.1%) and OC in 9 patients (27%). Lung hyperinflation was present in 15 patients, whilst the mean mMRC score was 2.2 ± 1.0. Lung hyperinflation was associated with CC (r = 0.772, p = 0.001), OC (r = 0.895, p = 0.001) and mMRC (r = 0.444, p = 0.010). CONCLUSIONS: Long COVID-19 patients present with small airways dysfunction and lung hyperinflation, which is associated with persistent dyspnoea, following hospitalisation.

The Impact of Cardiopulmonary Rehabilitation on Ventriculoarterial Coupling in Post-Coronavirus Disease-2019 Patients.

PURPOSE: Coronavirus disease-2019 (COVID-19) affects the cardiovascular system even after the acute phase of the disease. Cardiopulmonary rehabilitation may improve post-COVID-19 symptoms. This study aims to evaluate the impact of a cardiopulmonary rehabilitation program after acute COVID-19 on arterial stiffness, left ventricular function, and ventriculoarterial coupling (VAC). METHODS: Forty-eight adults were examined 1 (T0) and 3-mo (T1) following recovery from COVID-19 and randomized 1:1 to participate or not in a 3-mo rehabilitation program. Matched subjects were enrolled as a non-COVID-19 group. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (PWV). Left ventricular (LV) systolic performance was evaluated with global longitudinal strain (GLS). The PWV/LV-GLS ratio was calculated as an index of VAC. High-sensitivity C reactive protein (hs-CRP) was measured. RESULTS: At T0, convalescent patients with COVID-19 had impaired PWV ( P = .001) and reduced VAC ( P = .001) compared to non-COVID-19 subjects. PWV (8.15 ± 1.37 to 6.55 ± 0.98 m/sec, P < .001) and LV-GLS (-19.67 ± 1.98 to -21.3 ± 1.93%, P < .001) improved only in convalescent patients with COVID-19 undergoing rehabilitation. Similarly, VAC was only improved in the rehabilitation group (-0.42 ± 0.11 to -0.31 ± 0.06 m · sec -1  ·% -1 , P < .001). A significant improvement in VO 2max was noted after rehabilitation (15.70 [13.05, 21.45] to 18.30 [13.95, 23.75] ml · kg -1  · min -1 , P = .01). Finally, hs-CRP was improved in both groups with a significantly greater improvement in the rehabilitation group. CONCLUSION: A 3-mo rehabilitation program in convalesced patients with COVID-19 enhances the recovery of arterial stiffness, left ventricular function, and VAC, highlighting the beneficial mechanisms of rehabilitation in this patient population.

Exercise Intolerance Is Associated with Cardiovascular Dysfunction in Long COVID-19 Syndrome.

Background/Objectives: Cardiorespiratory complications are commonly reported among patients with long COVID-19 syndrome. However, their effects on exercise capacity remain inconclusive. We investigated the impact of long COVID-19 on exercise tolerance combining cardiopulmonary exercise testing (CPET) with resting echocardiographic data. Methods: Forty-two patients (55 ± 13 years), 149 ± 92 days post-hospital discharge, and ten healthy age-matched participants underwent resting echocardiography and an incremental CPET to the limit of tolerance. Left ventricular global longitudinal strain (LV-GLS) and the left ventricular ejection fraction (LVEF) were calculated to assess left ventricular systolic function. The E/e' ratio was estimated as a surrogate of left ventricular end-diastolic filling pressures. Tricuspid annular systolic velocity (SRV) was used to assess right ventricular systolic performance. Through tricuspid regurgitation velocity and inferior vena cava diameter, end-respiratory variations in systolic pulmonary artery pressure (PASP) were estimated. Peak work rate (WRpeak) and peak oxygen uptake (VO2peak) were measured via a ramp incremental symptom-limited CPET. Results: Compared to healthy participants, patients had a significantly (p < 0.05) lower LVEF (59 ± 4% versus 49 ± 5%) and greater left ventricular end-diastolic diameter (48 ± 2 versus 54 ± 5 cm). In patients, there was a significant association of E/e' with WRpeak (r = -0.325) and VO2peak (r = -0.341). SRV was significantly associated with WRpeak (r = 0.432) and VO2peak (r = 0.556). LV-GLS and PASP were significantly correlated with VO2peak (r = -0.358 and r = -0.345, respectively). Conclusions: In patients with long COVID-19 syndrome, exercise intolerance is associated with left ventricular diastolic performance, left ventricular end-diastolic pressure, PASP and SRV. These findings highlight the interrelationship of exercise intolerance with left and right ventricular performance in long COVID-19 syndrome.

ERS International Congress 2023: highlights from the Respiratory Clinical Care and Physiology Assembly.

It is a challenge to keep abreast of all the clinical and scientific advances in the field of respiratory medicine. This article contains an overview of laboratory-based science, clinical trials and qualitative research that were presented during the 2023 European Respiratory Society International Congress within the sessions from the five groups of Assembly 1 (Respiratory Clinical Care and Physiology). Selected presentations are summarised from a wide range of topics: clinical problems, rehabilitation and chronic care, general practice and primary care, electronic/mobile health (e-health/m-health), clinical respiratory physiology, exercise and functional imaging.

Epidemiology and Immunopathogenesis of Virus Associated Asthma Exacerbations.

Asthma is a common airway disease, affecting millions of people worldwide. Although most asthma patients experience mild symptoms, it is characterized by variable airflow limitation, which can occasionally become life threatening in the case of a severe exacerbation. The commonest triggers of asthma exacerbations in both children and adults are viral infections. In this review article, we will try to investigate the most common viruses triggering asthma exacerbations and their role in asthma immunopathogenesis, since viral infections in young adults are thought to trigger the development of asthma either right away after the infection or at a later stage of their life. The commonest viral pathogens associated with asthma include the respiratory syncytial virus, rhinoviruses, influenza and parainfluenza virus, metapneumovirus and coronaviruses. All these viruses exploit different molecular pathways to infiltrate the host. Asthmatics are more prone to severe viral infections due to their unique inflammatory response, which is mostly characterized by T2 cytokines. Unlike the normal T1 high response to viral infection, asthmatics with T2 high inflammation are less potent in containing a viral infection. Inhaled and/or systematic corticosteroids and bronchodilators remain the cornerstone of asthma exacerbation treatment, and although many targeted therapies which block molecules that viruses use to infect the host have been used in a laboratory level, none has been yet approved for clinical use. Nevertheless, further understanding of the unique pathway that each virus follows to infect an individual may be crucial in the development of targeted therapies for the commonest viral pathogens to effectively prevent asthma exacerbations. Finally, biologic therapies resulted in a complete change of scenery in the treatment of severe asthma, especially with a T2 high phenotype. All available data suggest that monoclonal antibodies are safe and able to drastically reduce the rate of viral asthma exacerbations.

Defining response to therapy with biologics in severe asthma: from global evaluation to super response and remission.

INTRODUCTION: In recent years, monoclonal antibodies targeting Type-2 inflammatory pathways have been developed for severe asthma treatment. However, even when patients are carefully selected, the response to treatment varies. AREAS COVERED: Different studies have evaluated response to therapy with biologics such as exacerbation reduction, symptom improvement, pulmonary function increase, improvement in QoL, or decrease of oral corticosteroids, showing that all patients do not respond to all disease aspects and leading to an extensive debate regarding the definition of response. EXPERT OPINION: Assessing response to therapy is of great importance, but since there is no uniform definition of treatment response, the recognition of patients who really benefit from these therapies remains an unmet need. In the same context, identifying non-responding patients in which biologic therapy should be switched or substituted by alternative treatment options is of paramount importance. In this review, we present the road trip of the definition of therapeutic response to biologics in severe asthmatics by presenting the current relevant medical literature. We also present the suggested predictors of response, with an emphasis on the so-called super-responders. Finally, we discuss the recent insights regarding asthma remission as a feasible treatment goal and provide a simple algorithm for the evaluation of response.

The Role of Rehabilitation in Arterial Function Properties of Convalescent COVID-19 Patients.

Coronavirus disease (COVID-19) is a respiratory disease, although arterial function involvement has been documented. We assess the impact of a post-acute COVID-19 rehabilitation program on endothelium-dependent vasodilation and arterial wall properties. We enrolled 60 convalescent patients from COVID-19 and one-month post-acute disease, who were randomized at a 1:1 ratio in a 3-month cardiopulmonary rehabilitation program (study group) or not (control group). Endothelium-dependent vasodilation was evaluated by flow-mediated dilation (FMD), and arterial wall properties were evaluated by carotid-femoral pulse wave velocity (cf-PWV) and augmentation index (AIx) at 1 month and at 4 months post-acute disease. FMD was significantly improved in both the study (6.2 ± 1.8% vs. 8.6 ± 2.4%, p < 0.001) and control groups (5.9 ± 2.2% vs. 6.6 ± 1.8%, p = 0.009), but the improvement was significantly higher in the study group (rehabilitation) (p < 0.001). PWV was improved in the study group (8.2 ± 1.3 m/s vs. 6.6 ± 1.0 m/s, p < 0.001) but not in the control group (8.9 ± 1.8 m/s vs. 8.8 ± 1.9 m/s, p = 0.74). Similarly, AIx was improved in the study group (25.9 ± 9.8% vs. 21.1 ± 9.3%, p < 0.001) but not in the control group (27.6 ± 9.2% vs. 26.2 ± 9.8 m/s, p = 0.15). Convalescent COVID-19 subjects of the study group (rehabilitation) with increased serum levels of circulating IL-6 had a greater reduction in FMD. Conclusively, a 3-month cardiopulmonary post-acute COVID-19 rehabilitation program improves recovery of endothelium-dependent vasodilation and arteriosclerosis.

Evaluation of the Acid-Base Status in Patients Admitted to the ICU Due to Severe COVID-19: Physicochemical versus Traditional Approaches.

BACKGROUND: Stewart's approach is known to have better diagnostic accuracy for the identification of metabolic acid-base disturbances compared to traditional methods based either on plasma bicarbonate concentration ([HCO3-]) and anion gap (AG) or on base excess/deficit (BE). This study aimed to identify metabolic acid-base disorders using either Stewart's or traditional approaches in critically ill COVID-19 patients admitted to the ICU, to recognize potential hidden acid-base metabolic abnormalities and to assess the prognostic value of these abnormalities for patient outcome. METHODS: This was a single-center retrospective study, in which we collected data from patients with severe COVID-19 admitted to the ICU. Electronical files were used to retrieve data for arterial blood gases, serum electrolytes, and proteins and to derive [HCO3-], BE, anion gap (AG), AG adjusted for albumin (AGadj), strong ion difference, strong ion gap (SIG), and SIG corrected for water excess/deficit (SIGcorr). The acid-base status was evaluated in each patient using the BE, [HCO3-], and physicochemical approaches. RESULTS: We included 185 patients. The physicochemical approach detected more individuals with metabolic acid-base abnormalities than the BE and [HCO3-] approaches (p < 0.001), and at least one acid-base disorder was recognized in most patients. According to the physicochemical method, 170/185 patients (91.4%) had at least one disorder, as opposed to the number of patients identified using the BE 90/186 (48%) and HCO3 62/186 (33%) methods. Regarding the derived acid-base status variables, non-survivors had greater AGadj, (p = 0.013) and SIGcorr (p = 0.035) compared to survivors. CONCLUSIONS: The identification of hidden acid-base disturbances may provide a detailed understanding of the underlying conditions in patients and of the possible pathophysiological mechanisms implicated. The association of these acid-base abnormalities with mortality provides the opportunity to recognize patients at increased risk of death and support them accordingly.

ERS International Congress 2022: highlights from the Respiratory Clinical Care and Physiology Assembly.

It is a challenge to keep abreast of all the clinical and scientific advances in the field of respiratory medicine. This article contains an overview of the laboratory-based science, clinical trials and qualitative research that were presented during the 2022 European Respiratory Society International Congress within the sessions from the five groups of Assembly 1 (Respiratory Clinical Care and Physiology). Selected presentations are summarised from a wide range of topics: clinical problems, rehabilitation and chronic care, general practice and primary care, mobile/electronic health (m-health/e-health), clinical respiratory physiology, exercise and functional imaging.