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Abstract Restrictive lung disease is a broad term encompassing a number of conditions in which lung volumes are reduced. Dyspnea is a common clinical manifestation of restrictive lung disease and frequently becomes a prominent and disabling symptom that undermines patients' ability to function and engage in activities of daily living (especially in those with more advanced restriction). Effective management of this disabling symptom awaits a better understanding of its underlying physiology. In recent decades, our understanding of the mechanisms of dyspnea in restrictive lung disease has been improved by a small, but significant, body of research. One approach to the study of dyspnea is to identify the major qualitative dimensions of the symptom in an attempt to uncover different underlying neurophysiologic mechanisms. This article will review the existing literature on the intensity and qualitative dimensions of dyspnea during exercise in patients with restrictive lung disease. The main focus will be on interstitial lung disease (ILD), since it is the prototypical restrictive disease.

Interstitial lung diseases (ILDs) are diverse parenchymal pulmonary disorders, primarily characterised by alveolar and interstitial inflammation and/or fibrosis, and sharing pathophysiological similarities. Thus, patients generally harbour common respiratory symptoms, lung function abnormalities and modified exercise adaptation. The most usual and disabling complaint is exertional dyspnoea, frequently responsible for premature exercise interruption. Cardiopulmonary exercise testing (CPET) is increasingly used for the clinical assessment of patients with ILD. This is because exercise performance or dyspnoea on exertion cannot reliably be predicted by resting pulmonary function tests. CPET, therefore, provides an accurate evaluation of functional capacity on an individual basis. CPET can unmask anomalies in the integrated functions of the respiratory, cardiovascular, metabolic, peripheral muscle and neurosensory systems in ILDs. CPET uniquely provides an evaluation of all above aspects and can help clinicians shape ILD patient management. Preliminary evidence suggests that CPET may also generate valuable prognostic information in ILDs and can be used to shed light on the presence of associated pulmonary hypertension. This review aims to provide comprehensive and updated evidence concerning the clinical utility of CPET in ILD patients, with particular focus on the physiological and clinical value of ventilatory efficiency (V˙E/V˙CO2).

Cystic fibrosis, due to the absence or abnormal function of the cystic fibrosis transmembrane conductance regulator, is the most common life-limiting autosomal recessive genetic disorder among the Caucasian population. The lungs are particularly affected due to thick and tenacious mucus causing parenchymal anomalies ranging from bronchiectasis, progressive airflow limitation, respiratory infections, lung destruction and ultimately respiratory failure. Despite the remarkable advances in treatment that have greatly improved survival, most patients experience progressive exercise curtailment, with the consequence that a growing number of patients with cystic fibrosis will be referred for exercise-based evaluations in the forthcoming years. Cardiopulmonary exercise testing, in particular, is a useful tool to assess the mechanisms of exercise intolerance in individual patients that may have treatment and prognostic implications. In this review, we will focus on ventilatory efficiency and its clinical and prognostic value in adults with cystic fibrosis.

Coronavirus disease 2019 (COVID-19) is a disease caused by a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-​2), and the predisposing and protecting factors have not been fully elucidated. COVID-19 primarily impacts the respiratory system, and can result in mild illness or serious disease leading to critical illness requiring admission to the intensive care unit due to respiratory failure. After hospital discharge, the more commonly described pulmonary function anomalies are alterations in diffusing capacity and the loss of lung volume. Reduction of inspiratory muscle contraction may also be underestimated. This article will focus on the pathophysiology of pulmonary function anomalies in COVID-19 survivors. We will discuss current advances and provide future directions and also present our perspective on this field.

Cardiopulmonary exercise testing (CPET) is a frequently used tool in the differential diagnosis of dyspnoea. Ventilatory inefficiency, defined as high minute ventilation (V′E) relative to carbon dioxide output (V′CO2), is a hallmark characteristic of pulmonary vascular diseases, which contributes to exercise intolerance and disability in these patients. The mechanisms of ventilatory inefficiency are multiple and include high physiologic dead space, abnormal chemosensitivity and an altered carbon dioxide (CO2) set-point. A normal V′E/V′CO2 makes a pulmonary vascular disease such as pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) unlikely. The finding of high V′E/V′CO2 without an alternative explanation should prompt further diagnostic testing to exclude PAH or CTEPH, particularly in patients with risk factors, such as prior venous thromboembolism, systemic sclerosis or a family history of PAH. In patients with established PAH or CTEPH, the V′E/V′CO2 may improve with interventions and is a prognostic marker. However, further studies are needed to clarify the added value of assessing ventilatory inefficiency in the longitudinal follow-up of patients.

Cardiopulmonary exercise testing (CPET) has long been used as diagnostic tool for cardiac diseases. During recent years CPET has been proven to be additionally useful for 1) distinguishing between normal and abnormal responses to exercise; 2) determining peak oxygen uptake and level of disability; 3) identifying factors contributing to dyspnoea and exercise limitation; 4) differentiating between ventilatory (respiratory mechanics and pulmonary gas exchange), cardiovascular, metabolic and peripheral muscle causes of exercise intolerance; 5) identifying anomalies of ventilatory (respiratory mechanics and pulmonary gas exchange), cardiovascular and metabolic systems, as well as peripheral muscle and psychological disorders; 6) screening for coexistent ischaemic heart disease, peripheral vascular disease and arterial hypoxaemia; 7) assisting in planning individualised exercise training; 8) generating prognostic information; and 9) objectively evaluating the impact of therapeutic interventions. As such, CPET is an essential part of patients' clinical assessment. This article belongs to the special series on the “Ventilatory efficiency and its clinical prognostic value in cardiorespiratory disorders”, addressed to clinicians, physiologists and researchers, and aims at encouraging them to get acquainted with CPET in order to help and orient the clinical decision concerning individual patients.

The objective of this document was to standardise published cardiopulmonary exercise testing (CPET) protocols for improved interpretation in clinical settings and multicentre research projects. This document: 1) summarises the protocols and procedures used in published studies focusing on incremental CPET in chronic lung conditions; 2) presents standard incremental protocols for CPET on a stationary cycle ergometer and a treadmill; and 3) provides patients' perspectives on CPET obtained through an online survey supported by the European Lung Foundation. We systematically reviewed published studies obtained from EMBASE, Medline, Scopus, Web of Science and the Cochrane Library from inception to January 2017. Of 7914 identified studies, 595 studies with 26 523 subjects were included. The literature supports a test protocol with a resting phase lasting at least 3 min, a 3-min unloaded phase, and an 8- to 12-min incremental phase with work rate increased linearly at least every minute, followed by a recovery phase of at least 2–3 min. Patients responding to the survey (n=295) perceived CPET as highly beneficial for their diagnostic assessment and informed the Task Force consensus. Future research should focus on the individualised estimation of optimal work rate increments across different lung diseases, and the collection of robust normative data.

Exertional dyspnoea is among the dominant symptoms in patients with chronic heart failure and progresses relentlessly as the disease advances, leading to reduced ability to function and engage in activities of daily living. Effective management of this disabling symptom awaits a better understanding of its underlying physiology. Cardiovascular factors are believed to play a major role in dyspnoea in heart failure patients. However, despite pharmacological interventions, such as vasodilators or inotropes that improve central haemodynamics, patients with heart failure still complain of exertional dyspnoea. Clearly, dyspnoea is not determined by cardiac factors alone, but likely depends on complex, integrated cardio-pulmonary interactions. A growing body of evidence suggests that excessively increased ventilatory demand and abnormal “restrictive” constraints on tidal volume expansion with development of critical mechanical limitation of ventilation, contribute to exertional dyspnoea in heart failure. This article will offer new insights into the pathophysiological mechanisms of exertional dyspnoea in patients with chronic heart failure by exploring the potential role of the various constituents of the physiological response to exercise and particularly the role of abnormal ventilatory and respiratory mechanics responses to exercise in the perception of dyspnoea in patients with heart failure.

Asthma is a chronic inflammatory disorder of the airways that leads to acute symptoms, exacerbations and sometimes, for a small part of the asthmatic population, fatal or near-fatal exacerbations. This as yet significant minority of individuals present with severe asthma and have persisting daily symptoms, and exacerbations despite compliance with high doses of inhaled steroids and additional treatment. For more than a decade, the pharmacological management of patients with severe asthma has focused on evaluating specific cytokines. The rationale of this approach is based on the distinguished key role played by eosinophils in the asthma inflammatory processes. Eosinophils are recruited from the circulation to airways where they cause airway damage via different mechanisms. Eosinophils are regulated in terms of their recruitment, activation, growth, differentiation and survival by interleukin (IL)-5. Abundant data from in vitro experiments, animal models and clinical trials has confirmed that IL-5 inhibition may be an effective approach for the treatment of asthma, especially severe asthma. Interfering with eosinophil function or reducing their numbers has been one of the most important goals of therapeutic monoclonal antibodies, which target cytokine receptor interactions in asthma, particularly IL-5. This review will consider new treatments options for severe asthma, particularly those targeting IL-5, that have already been evaluated in clinical trials in asthmatic patients.

Lung hyperinflation commonly accompanies expiratory flow limitation in patients with chronic obstructive pulmonary disease (COPD) and contributes importantly to morbidity and an impoverished quality of life. It is not surprising, therefore, that lung hyperinflation has become an important therapeutic target in symptomatic COPD patients. Acute dynamic increases in lung hyperinflation under conditions of worsening expiratory flow limitation and increased ventilatory demand (or both) can seriously stress cardiopulmonary reserves in patients with more advanced disease. The present understanding of the physiological mechanisms of dynamic hyperinflation during exacerbations of COPD and during physical activity continues to grow, together with an appreciation of its negative mechanical and sensory consequences. In this brief overview, definitions and measurement of lung hyperinflation during rest and exercise will be discussed and its potential clinical importance will be considered. The focus will mainly be on current concepts of the mechanisms of air trapping and its role in inducing respiratory discomfort and activity limitation in COPD.

Improvement in airway function in response to bronchodilator therapy is generally confirmed by simple spirometry. However, improvements in maximal expiratory flow rates have been shown to correlate poorly with important patient-centred outcomes, such as reduced exertional dyspnoea and improved exercise performance. Recent studies have suggested that attendant reductions in end-expiratory lung volume as a result of bronchodilator-induced improvements in lung emptying may be more closely associated with symptom relief and increased exercise capacity than traditional spirometric indices. To the extent that chronic lung hyperinflation and the superimposition of acute dynamic hyperinflation (in response to increased ventilation or expiratory flow limitation) result in excessive loading and weakening of the inspiratory muscles, then pharmacological lung volume reduction should have important mechanical and sensory benefits for the patient. The present article will examine the mechanisms of lung deflation following short-term bronchodilator therapy. The physiological links between reduced hyperinflation, improved dyspnoea and exercise endurance will be examined, and the emerging evidence for the additive effects of combining various modern pharmacological therapies will be reviewed.