Chest Pain Variant Asthma: A Report of Two Cases
Chest pain variant asthma (CPVA) is an atypical presentation of asthma that often leads to misdiagnosis due to its unique clinical characteristics. Unlike typical asthma, which is characterized by recurrent episodes of wheezing, dyspnea, chest tightness, and coughing, CPVA primarily manifests as chest pain without the classic symptoms of asthma. This condition is frequently misdiagnosed as coronary artery disease (CAD), gastroesophageal reflux disease (GERD), or other conditions, leading to inappropriate treatments and prolonged patient suffering. This article presents two cases of CPVA, highlighting the clinical features, diagnostic challenges, and management strategies for this under-recognized asthma phenotype.
Case Presentations
Case 1: A 71-Year-Old Woman with Migratory Chest Pain
A 71-year-old woman presented with a 3-year history of migratory chest pain. The pain was non-pleuritic and primarily located in the upper left chest region. It was sometimes induced by physical activities such as climbing stairs and tended to subside spontaneously in summer but re-emerged in winter. The patient had no history of cough, wheezing, expectoration, or dyspnea. She was a non-smoker with no history of allergic rhinitis or family history of asthma. Three years prior, she was admitted to the cardiology department with suspected angina pectoris. However, all diagnostic tests, including myocardial enzymology, electrocardiography (ECG), exercise testing, and computed tomography (CT) of the coronary artery, were normal. Despite treatment with isosorbide dinitrate and metoprolol, her chest pain persisted.
Physical examination revealed normal findings, including a blood pressure of 105/68 mmHg, a pulse rate of 80 beats/min, and a respiratory rate of 18 breaths/min. Auscultation of the lungs revealed normal breathing sounds. Chest CT, ECG, complete blood counts, immunoglobulin E (IgE) concentration, and D-dimer concentration were also normal. Baseline pulmonary function testing (PFT) showed mild restrictive ventilatory dysfunction. After inhaling albuterol (400 mg), the patient demonstrated a 45.5% improvement in forced expiratory volume in 1 second (FEV1), returning to normal levels and confirming a diagnosis of asthma.
The patient was initially treated with inhaled formoterol and budesonide, and her chest pain subsided within 3 days. She discontinued therapy after 3 months but experienced a recurrence of pain the following autumn. In October 2019, she resumed using the inhaler, and PFT revealed small airway obstruction despite normal forced vital capacity (FVC) and FEV1.
Case 2: A 56-Year-Old Woman with an 8-Year History of Chest Pain
A 56-year-old woman presented with an 8-year history of chest pain, primarily located behind the sternum and often occurring in the evening. The pain was sometimes relieved by sitting forward and taking shallow breaths. The patient had no associated symptoms such as nausea, vomiting, diaphoresis, or tobacco use. She had mild allergic rhinitis but no family history of asthma. Eight years prior, she was diagnosed with CAD, but all diagnostic tests, including coronary artery and chest CT, ECG, myocardial enzymology, IgE, and D-dimer concentration, were normal. Treatment with clopidogrel and isosorbide dinitrate provided no relief. In 2018, she was diagnosed with choledocholithiasis and GERD and underwent endoscopic retrograde cholangiopancreatography and anti-reflux treatment, but her chest pain persisted.
On October 10, 2019, the patient underwent a methacholine inhalation challenge test. Baseline PFT was normal, but the methacholine challenge test revealed a significant bronchoconstrictive response, with a 37.2% decrease in FEV1 compared to baseline, confirming a diagnosis of asthma. She was treated with inhaled formoterol and budesonide, and PFT performed one month later showed improvements in both FEV1 and FVC (2.06 vs. 1.72 L and 2.44 vs. 2.02 L, respectively). Her symptoms subsided after two months of treatment.
Discussion
Clinical Characteristics of CPVA
CPVA is a distinct asthma phenotype characterized by chest pain as the primary symptom, often in the absence of wheezing, dyspnea, or persistent cough. The pain is typically non-pleuritic and may be migratory, as seen in Case 1, or localized behind the sternum, as in Case 2. The severity, frequency, duration, and onset time of chest pain can vary among patients. In some cases, the pain is induced by physical activity but cannot be relieved by anti-anginal medications, a key clue that distinguishes CPVA from CAD.
Diagnostic Challenges
CPVA is frequently misdiagnosed due to its atypical presentation. Patients are often evaluated for CAD, GERD, or other conditions, leading to unnecessary tests and treatments. The diagnosis of CPVA is confirmed through pulmonary function testing (PFT) and bronchial challenge tests. In Case 1, the diagnosis was established by documenting reversible airway obstruction with PFT, while in Case 2, a methacholine inhalation challenge test revealed significant bronchoconstriction.
Mechanisms Underlying Chest Pain in Asthma
The exact mechanism of chest pain in CPVA remains unclear. One hypothesis suggests that airway constriction triggers mechanoreceptors in the lungs and bronchi, leading to a sensation of chest tightness and pain. Another theory posits that breathing at a higher residual volume may stress rib joint mechanics, causing dull or sharp chest pain. Additionally, the unpredictability of asthma attacks and the chronic nature of the disease may contribute to anxiety and fear, exacerbating chest pain.
Seasonal Variations and Environmental Triggers
In Case 1, the patient’s symptoms were aggravated in winter and relieved spontaneously in summer. This seasonal variation is consistent with the effects of cold exposure on the respiratory tract. Skin cooling and inhalation of cold air can lead to unfavorable reflexive airway changes and hyperosmolality of the nasal and airway mucosa, triggering bronchoconstriction and chest pain.
Management and Treatment
Patients with CPVA should be treated similarly to those with typical asthma. Inhaled corticosteroids and long-acting bronchodilators are the mainstay of treatment. In Case 1, the patient’s chest pain subsided within 3 days of initiating therapy, while in Case 2, symptoms improved after two months of treatment. For some patients, chest pain may persist despite standard asthma treatments, suggesting the involvement of other mechanisms, such as leukotrienes. In such cases, leukotriene receptor antagonists may be effective.
Importance of Awareness and Early Diagnosis
Improving physicians’ awareness of CPVA is crucial to reducing misdiagnosis and ensuring appropriate treatment. Patients presenting with chest pain and negative findings on ECG or chest radiography should be evaluated for asthma, particularly if their symptoms are recurrent, paroxysmal, and reversible. PFT and bronchial challenge tests are essential tools for confirming the diagnosis.
Conclusion
CPVA is an under-recognized asthma phenotype characterized by chest pain as the primary symptom. The cases presented here highlight the diagnostic challenges and management strategies for this condition. Early recognition and appropriate treatment are essential to improving patient outcomes. Physicians should consider CPVA in the differential diagnosis of patients with unexplained chest pain, particularly when symptoms are recurrent and reversible. Further research is needed to better understand the mechanisms underlying CPVA and to develop standardized diagnostic and therapeutic guidelines.
doi.org/10.1097/CM9.0000000000001495
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