Background: ‘Long COVID’-associated dyspnoea may persist for months after SARS-CoV-2 infection. Among the causes of persistent dyspnoea, dysfunctional breathing (DB), defined as an erratic or inappropriate ventilation at rest or exercise, has been observed, but little is known about its occurrence and pathophysiology among individuals with ‘long COVID’. We aimed to describe the occurrence and identify clinical predictors of DB among patients following SARS-CoV-2 infection. Methods: Cardiopulmonary exercise testing (CPET) was performed in 51 SARS-CoV-2 patients (median age, 64 years (IQR, 15)); male, 66.7%) living with ‘long COVID’ and persistent dyspnoea. CPET was classified into three dominant patterns: respiratory limitation with gas exchange abnormalities (RL); normal CPET or O₂ delivery/utilisation impairment (D); and DB. Non-parametric and χ² tests were applied to analyse the association between CPET dominant patterns and demographics, pulmonary function tests and SARS-CoV-2 severity. Results: Among 51 patients, DB mostly without hyperventilation was found in 29.4% (n=15), RL in 54.9% (n=28) and D in 15.7% (n=8). When compared with RL individuals, patients with DB were younger, had significantly less severe initial infection, a better transfer capacity for carbon monoxide (median 85% (IQR, 28)), higher oxygen consumption (22.9 mL/min/kg (IQR, 5.5)), a better ventilatory efficiency slope (31.6 (IQR, 12.8)), and a higher SpO₂ (95% (IQR, 3)). Conclusions: Our findings suggest that DB without hyperventilation could be an important pathophysiological mechanism of disabling dyspnoea in younger outpatients following SARS-CoV-2 infection, which appears to be a feature of COVID-19 not described in other viral diseases.

Background: Dysfunctional breathing is increasingly recognised after SARS-CoV-2 infection, but the associated symptoms, functional impact and quality of life have not been systematically studied. Methods: This study describes a prospective case series of 48 patients with dysfunctional breathing based on compatible symptoms and an abnormal breathing pattern during cardiopulmonary exercise testing. Patients with underlying disease that could explain these symptoms were excluded. Median time from COVID-19 to evaluation was 212 (IQR 121) days. Self-administered questionnaires, including the Nijmegen questionnaire, Short-Form (36) Health Survey (SF-36), Hospital Anxiety and Depression Scale, modified Medical Research Council scale, post-COVID-19 Functional Scale, and specific long COVID symptoms, were the outcome measures. Results: On average, mean V’O₂ was preserved. Pulmonary function tests were within limits of normality. Hyperventilation, periodic deep sighs/erratic breathing and mixed types of dysfunctional breathing were diagnosed in 20.8%, 47.1% and 33.3% of patients, respectively. After dyspnoea, the five most frequent symptoms using the Nijmegen scale with a cut-off of ≥3 were faster/deeper breathing (75.6%), palpitations (63.8%), sighs (48.7%), unable to breathe deeply (46.3%) and yawning (46.2%). Median Nijmegen and Hospital Anxiety and Depression Scale scores were 28 (IQR 20) and 16.5 (IQR 11), respectively. SF-36 scores were lower than the reference value. Conclusions: Long COVID patients with dysfunctional breathing have a high burden of symptoms, functional impact and a low quality of life, despite no or negligible organic damage.

Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the causes of pulmonary hypertension (PH) and requires invasive measurement of the mean pulmonary artery pressure (mPAP) during right heart catheterisation (RHC) for the diagnosis. 4D flow MRI could provide non-invasive parameters to estimate the mPAP. Twenty-five patients with suspected CTEPH underwent cardiac MRI. Mean vortex duration (%), pulmonary distensibility, right ventricular volumes and function were measured using 4D flow MRI and cine sequences, and compared with the mPAP measured by RHC. The mPAP measured during RHC was 33 ± 16 mmHg (10–66 mmHg). PH (defined as mPAP > 20 mmHg) was present in 19 of 25 patients (76%). A vortical flow was observed in all but two patients (92%) on 4D flow images, and vortex duration showed good correlation with the mPAP (r = 0.805; p < 0.0001). Youden index analysis showed that a vortex duration of 8.6% of the cardiac cycle provided a 95% sensitivity and an 83% specificity to detect PH. Reliability for the measurement of vortex duration was excellent for both intra-observer ICC = 0.823 and inter-observer ICC = 0.788. Vortex duration could be a useful parameter to non-invasively estimate mPAP in patients with suspected CTEPH.

Background: Cardiac output determination is essential in precapillary pulmonary hypertension. While direct Fick is the gold standard, thermodilution is commonly used as the reference method. Moving to noninvasive methods would be highly beneficial for patients, avoiding repetitive invasive assessments. This systematic review followed 3 objectives: (1) assessing the validity of indirect Fick and thermodilution in precapillary pulmonary hypertension, (2) assessing the interchangeability of noninvasive cardiac output measurement methods against reference methods in precapillary pulmonary hypertension, and (3) detecting methodological heterogeneity in the included studies. Methods: We systematically reviewed the literature using medical databases and following PRISMA guidelines. We included articles comparing an invasive or noninvasive cardiac output measurement method with thermodilution or direct Fick in precapillary pulmonary hypertension patients. Cutoffs of limits of agreement and percentage error derived from the Bland and Altman graph were used to accept interchangeability. To study methodological heterogeneity, we extracted 9 quality criteria from all studies. Results: Eleven studies were included. None reached the suggested interchangeability criteria. The median number of the 9 assessed quality criteria was 2 with interquartile range (0–4). Conclusions: Further studies evaluating the reliability of thermodilution and the consequences of its use in precapillary pulmonary hypertension patients are necessary. No evidence supports the use of indirect Fick in precapillary pulmonary hypertension. The studied noninvasive methods could not be considered interchangeable with invasive methods. A robust methodology should be used to draw sensible conclusions.

High-flow nasal oxygen (HFNO) is a type of non-invasive advanced respiratory support that allows the delivery of high-flow and humidified air through a nasal cannula. It can deliver a higher inspired oxygen fraction than conventional oxygen therapy (COT), improves secretion clearance, has a small positive end-expiratory pressure, and exhibits a washout effect on the upper air space that diminishes dead space ventilation. HFNO has been shown to reduce the work of breathing in acute hypoxemic respiratory failure (AHRF) and has become an interesting option for non-invasive respiratory support. Evidence published before the COVID-19 pandemic suggested a possible reduction of the need for invasive mechanical ventilation compared to COT. The COVID-19 pandemic has resulted in a substantial increase in AHRF worldwide, overwhelming both acute and intensive care unit capacity in most countries. This triggered new trials, adding to the body of evidence on HFNO in AHRF and its possible benefits compared to COT or non-invasive ventilation. We have summarized and discussed this recent evidence to inform the best supportive strategy in AHRF both related and unrelated to COVID-19.

Group 3 pulmonary hypertension (PH) associated with lung disease is a common cause of PH and is associated with substantial morbidity and mortality. Multiple studies of pulmonary arterial hypertension (PAH) therapies in this population have demonstrated conflicting results regarding their safety and efficacy, and therefore the optimum treatment for this group is unknown. The INCREASE and PERFECT randomised, double-blind, placebo-controlled trials attempted to address this unmet need by exploring the role of inhaled treprostinil (iTRE) in PH associated with interstitial lung disease (PH-ILD) and PH associated with COPD (PH-COPD), respectively. In the INCREASE and PERFECT studies individuals were randomised to placebo or iTRE, which was administeredviaan ultrasonic, pulsed-delivery nebuliser to a maximum dose of 72 μg, four times a day. The INCREASE study randomised 326 subjects with PH-ILD over a 16-week period and met its primary endpoint of change in 6-min walk distance, with a treatment effect of +31.12 m (p<0.001). Reduced disease progression events and increased forced vital capacity were also reported in the treatment arm in apost hocanalysis. By contrast, the PERFECT study was stopped prematurely by the data and safety monitoring committee due to evidence that iTRE increased serious adverse events in subjects with PH-COPD. This journal club provides an overview of these important trials and highlights pertinent unanswered questions in this field.