Pulmonary Carcinoid Tumors as an Asthma Mimic: Diagnostic Challenges, Clinical Presentation, and Management Strategies

Asthma is highly prevalent and imposes a substantial burden on patients and healthcare systems. Management is based on inhaled corticosteroid-containing therapy, with additional controller treatments and biologic agents reserved for appropriately selected patients with difficult-to-treat or severe disease [7,8]. Before escalating therapy, particularly to biologics, clinicians should confirm the diagnosis of asthma and evaluate alternative causes of persistent respiratory symptoms [7,8].

Pulmonary carcinoid tumors are well-differentiated pulmonary neuroendocrine neoplasms classified as typical or atypical carcinoids. Although they generally have a more favorable prognosis than high-grade pulmonary neuroendocrine carcinomas, centrally located tumors may produce a wide range of respiratory manifestations and can be diagnostically challenging. Persistent asthma-like symptoms may reflect uncontrolled asthma, an incorrect diagnosis, comorbid disease, inadequate treatment, or an alternative process such as inducible laryngeal obstruction, bronchiectasis, COPD, foreign-body aspiration, or an endobronchial tumor.

Pulmonary carcinoid tumors may cause cough, wheezing, dyspnea, and recurrent pneumonia through partial or complete obstruction of a major airway. This review summarizes mechanisms underlying asthma-like presentations, identifies practical clinical clues that should prompt investigation for a focal endobronchial lesion, and reviews diagnostic and management strategies for pulmonary carcinoid tumors.

For this review, two clinically distinct scenarios should be separated. In a true asthma mimic, asthma-like symptoms arise from focal mechanical airway obstruction caused by the tumor and may improve substantially after the obstruction is relieved. In contrast, a carcinoid tumor may coexist with objectively confirmed asthma, in which case inflammatory airway symptoms can persist after tumor treatment. This distinction matters because asthma-directed anti-inflammatory therapy and biologic agents do not correct fixed mechanical obstruction from an endobronchial mass.

Prior reports on this topic have primarily emphasized diagnosis and surgery, with less attention to the accumulating literature supporting bronchoscopic (endoscopic) treatment as a parenchyma-sparing option in appropriately selected patients. The current review extends the existing literature by (1) synthesizing relevant red flags that help differentiate carcinoid tumor from asthma in a single table (Table 2), (2) presenting an algorithm that integrates these features into a logical diagnostic and therapeutic work-up (Figure 3), and (3) emphasizing that bronchoscopic treatment may be considered alongside surgical resection as a therapeutic option, an issue not previously addressed in asthma-mimic reviews.

A structured PubMed search was used specifically to identify the case-level literature summarized in Table 1. No publication-year restriction was applied; the reports identified for this case-level synthesis were published between 1993 and 2020. Search terms included combinations of “pulmonary carcinoid,” “bronchial carcinoid,” “asthma mimic,” “endobronchial tumor,” “refractory asthma,” and “unilateral wheezing,” and the search was limited to English-language reports. One reviewer screened all identified records against prospectively defined eligibility criteria (see Eligibility Criteria). Fourteen case-level reports, case series, or case reviews were identified; seven were included in Table 1 and seven were excluded (four for a clinically irrelevant scenario, two for adenoid cystic carcinoma of the trachea, and one for carcinoid syndrome without asthma-like features in a patient with COPD). Additional references used for epidemiology, diagnosis, and management were selected narratively. No protocol was registered, no formal systematic risk-of-bias assessment was performed, and no quantitative synthesis was undertaken. The search and screening process should therefore be interpreted as a transparent component of a narrative review rather than as a systematic review.

Eligible records were those that described patients with (a) a carcinoid tumor located within the pulmonary, bronchial, or tracheal region; (b) accompanying respiratory symptoms (wheeze, cough, dyspnea, and/or recurrent infection) diagnosed as, or clinically suspected to represent, asthma; and (c) a sufficient case description. Records were excluded if the described patients had a non-carcinoid endobronchial tumor, carcinoid syndrome without asthma-like features, non-English language, or abstract/conference presentations without a case description. The above criteria were generated prospectively, prior to commencing with the screening process.

Because no second independent screener was available, the same reviewer re-screened all 14 records in a second pass using the same prespecified eligibility criteria; classifications were identical on both passes. This repeat-screening approach provides an internal consistency check but cannot replace independent screening by a second reviewer and remains susceptible to selection bias.

Pulmonary carcinoid tumors are relatively indolent, well-differentiated neuroendocrine tumors with less aggressive behavior than high-grade pulmonary neuroendocrine carcinomas. According to the World Health Organization (WHO) classification of pulmonary neuroendocrine tumors, last updated in 2021, pulmonary carcinoids are divided into typical and atypical carcinoids based on mitotic counts and the presence or absence of necrosis: while typical carcinoids have less than 2 mitoses per 2 mm² and no necrosis, atypical carcinoids have 2–10 mitoses per 2 mm² and/or foci of necrosis; the latter also exhibit a higher likelihood of lymph node infiltration, recurrence, and metastasis [6,31].

The principal mechanism by which an endobronchial carcinoid can mimic asthma is focal mechanical narrowing of a major airway. Wheeze caused by a central lesion is often localized or unilateral, whereas asthma more typically produces diffuse, bilateral expiratory wheeze [9,10]. Reduced breath sounds on the affected side and recurrent infection distal to the same obstructed bronchus can provide additional clues. Importantly, unilateral wheeze is not specific to carcinoid; foreign bodies, mucus plugging, airway strictures, and other endobronchial masses can produce the same finding. Accordingly, persistent localized wheeze should prompt investigation for a focal structural lesion rather than be interpreted as a tumor-specific sign [1-3].

Because tumor-related airway obstruction is structural rather than purely bronchospastic, symptoms may respond poorly or incompletely to bronchodilator therapy; however, partial symptomatic improvement does not exclude an endobronchial carcinoid. Improvement can also occur after bronchoscopic or surgical removal of the obstructing lesion, independent of any effect on airway inflammation.

In addition, pulmonary carcinoid tumors can occasionally release serotonin and other bioactive mediators that contribute to bronchoconstriction; however, classic carcinoid syndrome is uncommon in pulmonary carcinoid tumors. These mediators can cause bronchospasm, flushing, diarrhea, or dyspnea and can exacerbate asthma symptoms when released [12]. Thus, because bronchial stenosis, superimposed infection, and release of mediators can each cause wheezing that is partially responsive to bronchodilators, carcinoid tumors cannot be reliably distinguished from asthma on the basis of clinical response to therapy [4].

Pulmonary carcinoid tumors are uncommon neoplasms that account for approximately 1-2% of primary lung cancers and 20-30% of pulmonary neuroendocrine tumors in commonly cited series [5]. Their reported incidence has increased over time, likely in part because of greater use of cross-sectional imaging and bronchoscopy [5]. Compared with many other primary lung cancers, pulmonary carcinoids occur in relatively younger patients and have a weaker association with cigarette smoking; absence of a smoking history should therefore not lower clinical suspicion when other features suggest an endobronchial lesion [5,13].

Typical carcinoids are generally indolent tumors with low mitotic activity, absent necrosis, and a lower frequency of lymph-node involvement than atypical carcinoids. In contrast, atypical carcinoids are associated with increased risk of lymph node metastases, tumor recurrence, and distant spread of the disease; therefore, correct histopathological diagnosis is critical [14].

Pulmonary carcinoids are often diagnosed in mid-adulthood but can occur across a broad age range. Their indolent growth and central airway location can lead to prolonged treatment for presumed asthma or recurrent pneumonia before endoscopic and pathologic evaluation establishes the diagnosis. More recent case literature continues to illustrate this diagnostic pattern [11].

Endobronchial carcinoids may cause cough, wheeze, dyspnea, recurrent infection, and airflow limitation through bronchial obstruction. Published reports also show that a carcinoid tumor and true asthma can coexist, further complicating interpretation of persistent respiratory symptoms.

Aydin et al. reported a 48-year-old woman with a 12-year history of asthma who had persistent wheeze and dyspnea despite high-dose inhaled corticosteroid/long-acting beta2-agonist therapy, montelukast, and systemic corticosteroids and was being considered for anti-IgE therapy [20]. Bronchoscopy and CT identified a left lower lobe endobronchial mass, and biopsy confirmed a typical carcinoid. Lobectomy relieved the tumor-related symptoms, although a later acute asthma exacerbation showed that asthma and carcinoid can coexist.

Becher et al. described unilateral wheeze as the presenting manifestation of a bronchial carcinoid confirmed by bronchoscopy [2]. Santra et al. reported severe dyspnea and wheeze initially managed as asthma before failure of conventional therapy prompted bronchoscopy and diagnosis of a bronchial carcinoid [21]. Biçer et al. described a patient with severe asthma and a coexisting bronchial carcinoid who presented with pneumomediastinum [22].

Davila et al. reported a broader series of bronchial carcinoid presentations that included cough, wheeze, hemoptysis, recurrent respiratory infections, and dyspnea [23]. Emeryk et al. described a 39-year-old man with approximately 10-11 months of persistent wheeze, hemoptysis, and cough despite inhaled beta2-agonists and corticosteroids; bronchoscopy demonstrated an obstructing left-main-bronchus carcinoid [24]. Rizk et al. reported a 25-year-old woman treated for presumed asthma for approximately 1 year before CT and rigid bronchoscopy identified and removed a polypoid left-main-bronchus lesion, which was confirmed as a typical carcinoid [25].

Taken together, these reports show a recurring pattern: persistent or atypical asthma-like symptoms, especially when accompanied by localized wheeze, hemoptysis, recurrent focal infection, unexpected imaging, or inadequate response to appropriate therapy, should prompt reconsideration of the diagnosis. Targeted chest imaging and, when indicated, bronchoscopy are more appropriate than simply escalating asthma therapy when a focal structural lesion is suspected.

Because case reports are inherently susceptible to selective reporting, six individually reported cases in Table 1 were appraised against four reporting domains adapted from the CARE case-report guideline [29]: patient demographics, diagnostic work-up, treatment, and post-treatment outcome/follow-up. Davila et al. is an aggregate case series/review and was therefore not assessed with this single-case reporting checklist. This appraisal reflects the information available during screening (primarily abstract-level for several reports) and was intended to describe reporting completeness rather than methodological quality or risk of bias; it should not be interpreted as a substitute for a formal risk-of-bias tool.

Among the six individually appraised cases, only Aydin et al. reported a clearly described post-treatment outcome/follow-up in the material available for this review. The remaining reports primarily documented diagnosis and treatment without detailed long-term follow-up. This limitation in outcome reporting is addressed further in the Limitations section.

Symptoms of pulmonary carcinoid tumors depend on tumor location, degree of bronchial obstruction, and disease extent. Tumors may be entirely asymptomatic and found incidentally, or they may produce obstructive symptoms of the lower respiratory tract, including:

- Chronic cough - Wheezing - Shortness of breath - Frequent respiratory infections - Hemoptysis - Airway obstruction

Wheezing is particularly misleading because it readily suggests asthma. Tumor-related wheeze, however, is often localized and may have a focal correlate on imaging or bronchoscopy. It often responds incompletely to standard asthma treatment, although partial improvement with bronchodilators does not exclude an endobronchial carcinoid.

Clinical features that should raise suspicion for a carcinoid tumor rather than asthma include: obstructive symptoms presenting for the first time in adulthood; persistent wheeze that is unresponsive or only partially responsive to asthma medications; localized wheeze, asymmetric decreased breath sounds, or recurrent infection confined to the same lung region; and unilateral wheezing.

A progressive course of asthma-like symptoms that does not respond to treatment can be a reason for suspicion itself. While asthma is a chronic disease with a variable course, a carcinoid tumor can lead to progressive obstruction if left untreated. Unilateral or localized wheeze is a sign of focal airway obstruction of any cause (a finding not specific to carcinoid tumor) and the value of such a discovery lies in obtaining imaging and bronchoscopy, not in the confirmation of a specific etiology.

Diagnosis of a pulmonary carcinoid tumor relies on clinical assessment together with pulmonary function testing, radiographic imaging, bronchoscopy, and histopathology (Table 3).

Before diagnosing severe or refractory asthma, clinicians should confirm the diagnosis objectively when feasible, since misdiagnosis exposes patients to unnecessary corticosteroids, biologics, and repeated emergency visits. Studies of patients referred for severe asthma evaluation have found that a meaningful proportion did not, in fact, have asthma, which explained their lack of response to treatment [15]. Objective testing includes spirometry to demonstrate variable airflow obstruction, bronchodilator response, peak expiratory flow variability, and assessment of airway inflammation where applicable. Severe asthma should be diagnosed only after other conditions that could account for the symptoms have been considered.

Chest radiography may be normal or may show hilar airspace disease, atelectasis, recurrent focal infiltrates, or signs of post-obstructive infection; a normal film does not exclude an endobronchial lesion. Contrast-enhanced chest CT is an appropriate next step when a focal structural lesion is suspected and can demonstrate pulmonary carcinoid tumors, which are often hypervascular and enhance intensely. Characteristic CT findings include a well-defined hilar or perihilar mass, bronchial obstruction with distal atelectasis, mucus plugging, post-obstructive pneumonia, and, when present, regional lymphadenopathy. Small endobronchial lesions can nonetheless be missed on CT, so bronchoscopy remains necessary in selected patients [16].

Bronchoscopy is central to the evaluation of suspected endobronchial carcinoid tumors because it permits direct visualization of the airway, assessment of the extent of obstruction, and tissue sampling when clinically appropriate. Typical carcinoids appear as smooth, rounded, highly vascular endobronchial masses; because of this vascularity, biopsy should be performed cautiously to avoid significant bleeding. Histopathology with immunohistochemistry for neuroendocrine markers such as chromogranin A and synaptophysin confirms the diagnosis and distinguishes typical from atypical carcinoids [17], a distinction that carries direct implications for treatment and prognosis.

Note: The final step of treatment depicted in this figure (surgical resection) is the reference standard; the management section below describes an additional therapeutic option, namely bronchoscopic/endoscopic therapy for strictly intraluminal, typical carcinoids in carefully selected patients.

Treatment depends on tumor type, location, stage, and the presence or absence of metastasis.

Surgical resection remains the preferred treatment for most localized, resectable pulmonary carcinoid tumors. In carefully selected patients, bronchoscopic techniques may serve as a parenchyma-sparing approach, particularly for strictly intraluminal typical carcinoids without radiologic evidence of bronchial-wall or parenchymal invasion. Approximately 20% of bronchial carcinoids have been described as purely intraluminal polypoid lesions potentially suitable for endobronchial treatment [10]. In the systematic review by Reuling et al., nine endobronchial-treatment studies and 43 surgical studies were identified; outcomes were favorable in selected patients, but the evidence was retrospective, non-randomized, and subject to selection bias [10]. Current guidance continues to favor complete surgical resection for most operable localized tumors, while reserving endobronchial treatment for selected situations, including patients unsuitable for surgery or as part of a staged strategy [10,30].

The bronchoscopic techniques that have been reported in the literature include rigid bronchoscopy with mechanical debulking, neodymium:YAG (Nd:YAG) laser photoresection, electrocautery or snare resection, argon plasma coagulation, cryotherapy, including cryorecanalization, and, more rarely, photodynamic therapy [26] (Table 4). Brokx et al. reported on long-term outcomes (follow-up duration of up to 5 years) after initial bronchoscopic therapy (with or without subsequent surgery) in patients with typical carcinoids and found that local tumor control was achieved in all patients who were appropriately selected [26]. In a series of 10 patients who underwent flexible bronchoscopic Nd:YAG laser photoresection of a carcinoid tumor under conscious sedation, no treatment-related complications were reported, and with a follow-up duration of 29 months, no recurrences were detected, albeit with multiple procedures being needed for tumor clearance [27]. The review by Reuling et al. cites a figure from another study reporting an 8% recurrence rate at 10 years after EBT and suggests that surgical salvage can be an option if recurrence develops [10] (Table 5).

Successful endobronchial management depends on careful patient selection. Favorable features include histologic confirmation of a typical carcinoid, a strictly intraluminal lesion with a clearly defined base or stalk, no radiologic or endobronchial-ultrasound evidence of extraluminal extension, no nodal or distant metastases, and the ability to adhere to bronchoscopic and radiologic surveillance [26-28]. Because small biopsies can underestimate tumor extent or histologic aggressiveness, bronchoscopic treatment may also function as an initial diagnostic and local-control strategy while preserving the option of definitive surgery if atypical histology, wall invasion, incomplete clearance, or recurrence is identified [26-28].

Complete surgical resection is the treatment of choice for localized pulmonary carcinoid tumors and is associated with excellent survival. The surgical approach is tailored to tumor size, location, airway involvement, and overall pulmonary function; centrally located tumors can often be managed with parenchyma-sparing techniques such as sleeve resection or bronchoplastic reconstruction rather than more extensive resection [18]. Options include:

- Sleeve resection - Bronchoplastic procedures - Lobectomy - Other resections tailored to tumor extent

Evaluation of regional lymph nodes is important, particularly for atypical carcinoids, to help establish disease stage. Table 6 summarizes the recommended treatment approach by clinical setting.

For unresectable tumors or distant metastases, options include somatostatin analogues, targeted therapy, and peptide receptor radionuclide therapy (PRRT) guided by somatostatin receptor imaging and individual tumor biology. The pivotal randomized trial that established PRRT efficacy was performed in midgut neuroendocrine tumors [19]; prospective and retrospective series specific to bronchial typical and atypical carcinoids have separately reported objective responses and disease control with ¹⁷⁷Lu-DOTATATE, with higher response rates in typical than in atypical carcinoids [32]. Care should be coordinated through a multidisciplinary team experienced in neuroendocrine lung tumors, and observation may be appropriate for select asymptomatic patients. Table 7 summarizes the key histologic and prognostic differences between typical and atypical carcinoids described throughout this review.

This review is based primarily on case reports, small case series, and narrative reviews rather than large comparative cohorts, reflecting the low overall incidence of pulmonary carcinoid tumors and the resulting scarcity of higher-quality evidence on their overlap with asthma. Publication bias likely favors atypical or diagnostically striking presentations over routine ones, which may overstate how distinctive the clinical features described here are in unselected populations. The recommendations on when to suspect an endobronchial tumor in a patient with presumed asthma are therefore based on expert opinion and accumulated case experience rather than prospective validation.

The evidence supporting bronchoscopic (endoscopic) treatment specifically is similarly limited to small, often single-center studies and one systematic review of a small number of studies; randomized comparisons of bronchoscopic and surgical treatments are lacking, and therefore the comparisons of outcomes described in this review should be regarded with caution.

Pulmonary carcinoid tumors are rare but should be part of the differential diagnosis in patients with asthma-like symptoms, since endobronchial obstruction can produce wheeze, cough, dyspnea, recurrent infection, and hemoptysis that closely mimic asthma. Because asthma is far more common than carcinoid tumors, the latter are often overlooked, and patients, including several described in this review, may be treated for years with escalating inhaled and systemic corticosteroids, or even considered for biologic therapy, before the correct diagnosis is made.

Clinicians should reassess the diagnosis in patients with treatment-resistant asthma rather than assuming refractory symptoms simply reflect more severe airway inflammation. Unilateral wheeze, asymmetric breath sounds, recurrent infection localized to one lung segment, unexpected radiographic findings, or hemoptysis should prompt further evaluation, typically with chest CT followed by bronchoscopy, although none of these findings is specific enough to confirm or exclude asthma on its own. Notably, asthma and a carcinoid tumor can coexist, and symptoms may persist after tumor resection if underlying asthma is also present, underscoring the need to distinguish obstruction from tumor mass from inflammation-driven airway disease, since the two require different treatment.

Diagnosis requires a multidisciplinary approach involving pulmonology, radiology, pathology, and thoracic surgery, with chest CT to identify endobronchial masses and post-obstructive changes and bronchoscopy with biopsy to confirm the diagnosis and distinguish typical from atypical carcinoid, which differ in prognosis and treatment.

Complete surgical resection remains the principal treatment for most localized, resectable disease, offering a generally favorable prognosis, but bronchoscopic (endoscopic) therapy appears to be a reasonable parenchyma-sparing option or initial approach for strictly intraluminal typical carcinoids in selected patients, with completion surgery for those with incomplete resection or atypical histology, and individualized systemic therapy for more advanced disease. Increased recognition of pulmonary carcinoid tumor as an entity that may mimic asthma and awareness of the therapeutic options for these tumors when the diagnosis is established may hasten the diagnostic process and improve patient care by diminishing the likelihood of both inappropriate escalation of therapy for asthma and unnecessary extent of surgery when the diagnosis is established.