Image Quizzes

History of nonproductive cough

Reviewed by Zab Mosenifar, MD

Wellcome Images / Science Source

A 42-year-old nonsmoking man presents with complaints of a 9-month history of wheezing, nonproductive cough, and exertional dyspnea. The patient reports nighttime awakenings from his symptoms three to five times per month. He was diagnosed with asthma by his primary care provider about 3 months after his symptoms began. On diagnosis, he was prescribed a short-acting beta-2 adrenergic agonist rescue inhaler and an inhaled corticosteroid (ICS), twice daily. Because the patient remained symptomatic, his primary care provider stepped up his daily therapy to a combined ICS and long-acting beta2-adrenergic agonist (LABA). At today's visit, the patient reports continued symptoms and use of his rescue inhaler at least twice per week. He has no other significant medical history aside from a history of mild atopic dermatitis. He is 5 ft 11 in and currently weighs 172 lb (BMI 24). He demonstrates proper inhaler technique and states that he is compliant with his therapy.

Physical examination reveals loud wheezing during inspiration and throughout expiration. The patient's heart rate is 110 beats/min; blood pressure is 130/70 mm Hg. Pulse oximetry is 93%. Spirometry reveals a forced expiratory volume in the first second (FEV1) of 78% predicted. Fractional exhaled nitric oxide (FeNO) is 56 ppb. Chest radiography is normal. High-resolution CT shows air trapping, mosaic lung attenuations, and bronchial wall thickening. IgE level is normal; sputum culture reveals 6% eosinophils.

What is the likely diagnosis?

Eosinophilic pneumonia

Bronchopulmonary aspergillosis

Eosinophilic asthma

Chronic obstructive pulmonary disease

The history and findings in this case are suggestive of eosinophilic asthma.

Asthma is a common, chronic, and heterogeneous respiratory disease, most often characterized by chronic airway inflammation. Affected individuals experience respiratory symptoms (ie, wheezing, dyspnea, chest tightness, and cough) that may fluctuate over time and in intensity, as well as variable expiratory airflow limitation, which may become persistent. For many patients, asthma has a significant impact on quality of life. According to the World Health Organization, asthma affected an estimated 262 million people and caused 455,000 deaths. Currently, approximately 334 million people worldwide are believed to be affected by asthma.

Asthma frequently begins in childhood, but adult-onset asthma can occur and often presents as a nonatopic and eosinophilic condition. In fact, asthma is an umbrella diagnosis that encompasses several diseases with distinct mechanistic pathways (endotypes) and variable clinical presentations (phenotypes), all of which manifest with respiratory symptoms and are accompanied by variable airflow obstruction.

Broadly, asthma endotypes are categorized as type 2 (T2)-high or T2-low. Eosinophilic asthma falls under the T2-high endotype and comprises three phenotypes: atopic, late-onset, and aspirin-exacerbated respiratory disease. Late-onset T2-high asthma is characterized by prominent blood and sputum eosinophilia and is refractory to inhaled/oral corticosteroid treatment. Patients in this subgroup tend to be older and have more severe asthma with fixed airflow obstruction and more frequent exacerbations; patients may also have comorbid chronic rhinosinusitis with nasal polyps, which usually precedes asthma development. High FeNO levels and normal or elevated serum total IgE levels are also often seen in this subgroup.

The late-onset eosinophilic asthma phenotype accounts for 20%-40% of severe asthma cases and is associated with rapid decline of respiratory functions. Thus, earlier escalation of therapy may be indicated in patients with this phenotype.

According to a 2022 report from the Global Initiative for Asthma, the possibility of refractory T2 asthma should be considered when any of the following is found in patients taking high-dose ICS or daily oral corticosteroids:

• Blood eosinophils ≥ 150/μL, and/or
• FeNO ≥ 20 ppb, and/or
• Sputum eosinophils ≥ 2%, and/or
• Asthma is clinically allergen driven

Biologic T2-targeted therapies are available as add-on therapies for patients with T2 airway inflammation and severe asthma despite taking at least a high-dose ICS-LABA, and who have eosinophilic or allergic biomarkers or need maintenance oral corticosteroids. Available options for eosinophilic asthma include anti-IL-5/anti-IL-5R therapies (benralizumab, mepolizumab, reslizumab) and anti-IL-4R therapy (dupilumab).

Zab Mosenifar, MD, Medical Director, Women's Lung Institute; Executive Vice Chairman, Department of Medicine, Cedars Sinai Medical Center, Los Angeles, California.

Zab Mosenifar, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

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