Pathophysiology and clinical evaluation of the patient with unexplained persistent dyspnea

ABSTRACT

Introduction

Dyspnea is a complex symptom, which largely results from an imbalance between an afferent sensory stimulus and the corresponding efferent respiratory neuromuscular response. In addition, it is heavily influenced by the patient’s prior experiences and sociocultural factors.

Areas covered

The diagnostic approach to these patients requires a graded, systematic, and often multidisciplinary approach to determine what is the underlying pathophysiologic process. Utilization of objective data obtained through lab testing, imaging, and advanced testing, such as cardiopulmonary exercise testing, is often required to help identify underlying pathology contributing to a patient’s symptoms. This article will review dyspnea’s underlying pathophysiological mechanisms and standardized approaches to diagnoses. In the expert opinion section, we will discuss our own clinical approach to evaluating patients with persistent dyspnea.

Expert opinion

Unexplained dyspnea is a challenging diagnosis that occurs in patients with and without underlying cardiopulmonary diseases. It requires a systematic approach, which initially uses clinical evaluation in addition to standard imaging and clinical biomarkers. When diagnoses are not made during the initial evaluation, subsequent tests can include cardiopulmonary exercise test and methacholine challenge. To be certain of the correct diagnosis, It is imperative that the clinician determines dyspnea’s response to a particular therapeutic intervention.

KEYWORDS:

• Dyspnea
• CPET
• deconditioning
• dysfunctional breathing
• exercise

Article highlights

• Persistent dyspnea is a common and debilitating symptom that affects up to 50% of patients admitted to hospitals and as many as 25% of those seeking care in outpatient facilities

• Dyspnea is a complex and frequently reported symptom. It is influenced by a patient’s culture, environment, individual perception, and past experiences. It may be the result of a dysfunctional breathing pattern or potentially herald an ominous diagnosis

• When the diagnosis is not obvious from the initial history and examination, additional testing should include pulmonary function testing with pre- and post-bronchodilator spirometry, chest & cardiac imaging, laboratory testing (complete blood count, arterial gases, thyroid stimulating hormone [TSH], brain natriuretic peptide [BNP]), and evaluation of bronchial hyperresponsiveness with methacholine testing. If the diagnosis is not made at this stage, cardiopulmonary exercise testing (CPET), can be useful to understand the underlying pathophysiology and narrowing the list of potential diagnoses

• Using a graded diagnostic approach that includes CPET has shown to yield a specific etiology for persistent unexplained dyspnea in 75 – 99% of patients

• Physical deconditioning, dysfunctional breathing, paradoxical vocal fold motion, and obesity are frequent causes for persistent unexplained dyspnea in patients with or without underlying cardiopulmonary diseases.

Declaration of interest

F. Holguin is a member of the adjudication committee for the INSMED ASPEN Bronsocatib trial and is a member of the FDA’s Pulmonary and Allergy Drug Committee. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was funded by the National Institutes of Health, Heart and Lung Blood Institute [Grant # 1 R01 HL146542-01].