Pulmonology approach in the investigation of chronic unexplained dyspnea

Abstract

Chronic unexplained dyspnea and exercise intolerance represent common, distressing symptoms in outpatients. Clinical history taking and physical examination are the mainstays for diagnostic evaluation. However, the cause of dyspnea may remain elusive even after comprehensive diagnostic evaluation-basic laboratory analyses; chest imaging; pulmonary function testing; and cardiac testing. At that point (and frequently before), patients are usually referred to a pulmonologist, who is expected to be the main physician to solve this conundrum. In this context, cardiopulmonary exercise testing (CPET), to assess physiological and sensory responses from rest to peak exercise, provides a unique opportunity to unmask the mechanisms of the underlying dyspnea and their interactions with a broad spectrum of disorders. However, CPET is underused in clinical practice, possibly due to operational issues (equipment costs, limited availability, and poor remuneration) and limited medical education regarding the method. To counter the latter shortcoming, we aspire to provide a pragmatic strategy for interpreting CPET results. Clustering findings of exercise response allows the characterization of patterns that permit the clinician to narrow the list of possible diagnoses rather than pinpointing a specific etiology. We present a proposal for a diagnostic workup and some illustrative cases assessed by CPET. Given that airway hyperresponsiveness and pulmonary vascular disorders, which are within the purview of pulmonology, are common causes of chronic unexplained dyspnea, we also aim to describe the role of bronchial challenge tests and the diagnostic reasoning for investigating the pulmonary circulation in this context.

Cardiopulmonary exercise testing to indicate increased ventilatory variability in subjects with dysfunctional breathing

“…The current study moved a step forward to objectively characterize the erratic breathing pattern described in subjects with DB during CPET (Neder et al, 2016). In the context of chronic, out‐of‐proportion dyspnoea without any CPET response indicative of an organic disease (Berton et al, 2021; Neder et al, 2018), f variability proved particularly useful to discriminate subjects with DB from healthy controls. Identifying DB has a relevant clinical impact vis‐à‐vis (a) reassurance for the patient, family, and caregivers concerning the nature of the condition, (b) reduction in health care costs and risks associated with futile—and potentially iatrogenic—additional investigations, and (c) establishment of a proper therapeutic plan (Boulding et al, 2016; Courtney 2009; Depiazzi and Everard 2016; Vidotto et al, 2019)…”

“…The current study moved a step forward to objectively characterize the erratic breathing pattern described in subjects with DB during CPET (Neder et al, 2016). In the context of chronic, out-ofproportion dyspnoea without any CPET response indicative of an organic disease (Berton et al, 2021;Neder et al, 2018) (Boulding et al, 2016;Courtney 2009;Depiazzi and Everard 2016;Vidotto et al, 2019) Currently, there are no standardized criteria to reliably indicate the erratic breathing pattern commonly described in patients with DB. (Courtney, van Dixhoorn, et al, 2011b;Ionescu et al, 2021;Neder et al, 2018;Prys-Picard et al, 2006;Thomas et al, 2001).…”

“…The data were retrospectively retrieved and analyzed from the CPETs performed at our clinical practice. The DB group comprised adults of both sexes who were referred for CPET due to persistent and clinically relevant dyspnoea (at least 3 months, modified Medical Research Council scale score ≥2) which remained unexplained after thorough clinical assessment, basic biochemical testing, complete blood count, thyroid function testing, pulmonary function testing and chest imaging (Berton et al, 2021). They were clinically stable for at least 8 weeks before inclusion and were not involved in regular exercise training.…”

“…Anthropometric, demographic and clinical data were extracted from the CPET requisition and electronic medical records. Moreover, they should present with: (a) an erratic breathing pattern by visual inspection with a trend to alternating surges in ventilatory parameters against time; (b) a clear dissociation between ventilation (V̇E) and metabolic demand as indicated by large variations in V̇E/carbon dioxide output (V̇CO 2 ) accompanied by similar, but noncyclical, fluctuations in end‐tidal CO 2 pressure (PETCO 2 ); and (c) absence of any other abnormal patterns of exercise limitation (O 2 delivery/utilization impairment; mechanical ventilatory impairment; and/or gas‐exchange impairment) (Berton et al, 2021; Neder et al, 2018) and/or electrocardiographic abnormalities. Subjects were excluded if there was any clinical diagnosis that could potentially explain exertional dyspnoea, inability to perform a CPET, or cognitive impairment precluding the safe performance of study procedures.…”

The pulmonary function laboratory in the investigation of dyspnea of unknown origin

“…Note that the sequence can be modified on the basis of clinical impression and depending on local resources and expertise. Modified with permission from Berton et al 7 CBC: complete blood cell count; BNP: brain natriuretic peptide; BD: bronchodilator; MVV: maximal voluntary ventilation; ABGs: arterial blood gas analysis; V D /V T : dead space to tidal volume ratio; ECG: electrocardiography; CPET: cardiopulmonary exercise testing; V/Q: ventilation/perfusion; and CTPA: CT pulmonary angiography. …”