Introduction

Approximately 10% to 15% of asthma patients have refractory of severe asthma to regular medications. A careful workup should be done in these patients to exclude other comorbidities contributing to their uncontrolled asthma problems. In addition, there are various treatment options available to consider once underlying conditions are ruled out. This case represents a patient with uncontrolled asthma that remains refractory to medications despite using standard-of-care therapeutic options. Here is a case of 50y/female who complained of persistent wheeze and dyspnea. There is a need for an extensive workup to assess for comorbidities, confirm the diagnosis, and consider different treatment options (Dipaolo and Stull, 1993).

Case Report

A 48-year woman was admitted to our hospital complaining of dyspnea and wheezing. She has been a known case of asthma for 12years on regular medication and was well controlled using budesonide at 160 µg + formoterol at 4.5 µg b.i.d. combination therapy until five months back. However, five months back, she had a severe asthma attack associated with wheezing and had persisted for several months. She was treated with budesonide at 320 µg + formoterol at 9 µg b.i.d. combination, oral steroids (30–40 mg/day of prednisolone), and montelukast at 10 mg/day during that period, which was unsuccessful. Because her asthma had failed to come back under control, she was referred to our hospital and hospitalized for evaluation for anti-IgE therapy. In addition, she is taking thyroid hormone for Hashimoto's thyroiditis and calcium tablets for osteoporosis.

Her vitals were stable with a pulse rate of 86 bpm, a temp of 36.5°C, BP of 120/70 mmHg, and respiratory rate of 18/min on physical examination. Her examination was normal with except for decreased auscultation in the left lung.

Investigations and Management

Patient CBC showed normal values. Spirometry revealed an obstructive pattern (forced expiratory volume in 1 second [FEV1], 82%; forced vital capacity [FVC], 110%; FEV1/FVC, 60%). spirometric reversibility was not present, but she had a reversible airway obstruction at previous hospital admission. (prebronchodilator FEV1, 64%; postbronchodilator FEV1, 75%; reversibility, 17%). Her skin-prick test was positive for house-dust mites. The total IgE level was 115 kU/L. All data about the patient suggested that she could be a candidate for anti-IgE therapy. Chest X-ray revealed a left-sided hilar opacity. CT was performed for further evaluation and revealed a 15-mm nodular lesion at the left lower lobe bronchus. The radiological findings changed management and diagnosis from asthma to a chest mass. Fiberoptic bronchoscopy was done, which showed an endobronchial lesion obstructing the left lower bronchus lumen. As the lesion was highly vascularized and due to risk of bleeding biopsy was not performed. Bronchial lavage fluid was done from the left bronchus. Cytological examination of the lavage fluid revealed normal. She has undergone left lower lobectomy and mediastinal dissection.

Focal tumour invasion of the lung parenchyma through the bronchial wall was also noted. In addition, immunohistochemical staining revealed cytoplasmic positivity of pancytokeratin, CD56, chromogranin A and synaptophysin. These findings suggested the diagnosis of a typical carcinoid (TC) tumor.

After surgical resection, the patient is asymptomatic with budesonide at 160 µg + formoterol at 4.5 µg combination therapy and had a better pulmonary function (FEV1, 95%, FVC, 138%; FEV1/FVC, 59%). In addition, the patient had no recurrence for two years and her asthma is presently well controlled.

Discussion

Despite asthma patients treated with regular medications, many cases show recurrent attacks /flares. Proper workup to be done to evaluate other comorbidities that aggravate the symptoms of asthma-like carcinoid tumors, GERD, etc., and reconfirmation of asthma as diagnosis is required for appropriate treatment (Schrevens et al., 2004). Here we have a case of asthma with persistent wheeze and dyspnea after an acute flare of asthma, which on further evaluation diagnosed as carcinoid tumour.  Pulmonary carcinoid tumours are mostly misdiagnosed with asthma. The symptoms of pulmonary carcinoid tumours include hemoptysis, cough, wheeze, lower respiratory tract infections, only a few cases are diagnosed as carcinoid tumours co-exsisting with asthma. In this case, carcinoid tumour was diagnosed while working up the case (Marty et al., 1995). As it is a case of carcinoid tumour co-exsisting with asthma, and IgE are raised, the patient needs treatment with Anti-IgE therapy. The patient had recurrent attack of asthma after 8 months of surgery, hence the patient's diagnosis of asthma can be confirmed (Hurt and Bates, 1984; Turktas et al., 2010). Further detailed evaluation of the any uncontrolled asthma in spite of proper treatment is required to evaluate the cause and to provide appropriate treatment. Currently, the patient is symptomatically better and is on regular treatment for asthma.

Author contribution

Yogarajan R, Jayakumari S, Sumathi K and Mohan Kumar P R encouraged and supervised the findings of this work. All authors discussed the results and contributed to the final manuscript.

References

Agusti, A. G. N., Noguera, A., Sauleda, J., Sala, E., Pons, J., & Busquets, X. (2003). Systemic effects of chronic obstructive pulmonary disease. European Respiratory Journal, 21(2), 347-360.https://doi.org/10.1183/09031936.03.00405703

Bousquet, J., Khaltaev, N., Cruz, A. A., Denburg, J., Fokkens, W. J., Togias, A., ... & Zuberbier, T. (2008). Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA2LEN and AllerGen). Allergy, 63(S86), 8-160.https://doi.org/10.1111/j.1398-9995.2007.01620.x

Busse, W. W., & Lemanske, R. F. (2001). Asthma. The New England Journal of Medicine, 344(5), 350-362.https://doi.org/10.1056/NEJM200102013440507

Castro, M., Zangrilli, J., Wechsler, M. E., Bateman, E. D., Brusselle, G. G., Bardin, P., ... & Newbold, P. (2018). Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: A randomized, phase 3 study. Chest, 153(1), 132-140.

Chanez, P., Wenzel, S. E., Anderson, G. P., Anto, J. M., Bel, E. H., Boulet, L. P., ... & Sterk, P. J. (2007). Severe asthma in adults: What are the important questions? The Journal of Allergy and Clinical Immunology, 119(6), 1337-1348.https://doi.org/10.1016/j.jaci.2006.11.702

Chung, K. F., Wenzel, S. E., Brozek, J. L., Bush, A., Castro, M., Sterk, P. J., ... & Teague, W. G. (2014). International ERS/ATS guidelines on definition, evaluation, and treatment of severe asthma. The European Respiratory Journal, 43(2), 343-373.https://doi.org/10.1183/09031936.00202013

Dipaolo, F., & Stull, M. A. (1993). Bronchial carcinoid presenting as refractory asthma. American Family Physician, 48(6), 785-789.https://doi.org/10.1136/thx.48.8.789

Durrington, H. J., Farrow, S. N., Loudon, A. S., & Ray, D. W. (2014). The circadian clock and asthma. Thorax, 69(1), 90-92.https://doi.org/10.1136/thoraxjnl-2013-203482

GINA. (2022). Global Strategy for Asthma Management and Prevention. Global Initiative for Asthma (GINA). Retrieved from https://ginasthma.org/

Hekking, P. P. W., & Wener, R. R. (2015). The importance of correct asthma diagnosis in patients with persistent symptoms. The European Respiratory Journal, 46(5), 1324-1327.

Humbert, M., Busse, W., Hanania, N. A., Lowe, P. J., Canvin, J., Erpenbeck, V. J., & Holgate, S. (2014). Omalizumab in asthma: An update on recent developments. The Journal of Allergy and Clinical Immunology, 133(2), 546-552.https://doi.org/10.1016/j.jaip.2014.03.010

Hurt, R., & Bates, M. (1984). Carcinoid tumors of the bronchus: A 33-year experience. Thorax, 39(8), 617-623.https://doi.org/10.1136/thx.39.8.617

Kudo, M., Ishigatsubo, Y., & Aoki, I. (2013). Pathology of asthma. Frontiers in Microbiology, 4(263), 1-15.https://doi.org/10.3389/fmicb.2013.00263

Lambrecht, B. N., Hammad, H., & Fahy, J. V. (2019). The cytokines of asthma. Immunity, 50(4), 975-991.https://doi.org/10.1016/j.immuni.2019.03.018

Martinez, F. D. (2013). The origins of asthma and chronic obstructive pulmonary disease in early life. Proceedings of the American Thoracic Society, 10(2), 137-141.

Marty, H. C., Costes, V., & Pujol, L. J. (1995). Carcinoid tumors of the lung: Do atypical features require aggressive management? Annals of Thoracic Surgery, 59(1), 78-83.https://doi.org/10.1016/0003-4975(94)00630-P

Masoli, M., Fabian, D., Holt, S., & Beasley, R. (2004). The global burden of asthma: Executive summary of the GINA Dissemination Committee report. Allergy, 59(5), 469-478.https://doi.org/10.1111/j.1398-9995.2004.00526.x

McCracken, J. L., Tripple, J. W., Calhoun, W. J., & Ameredes, B. T. (2017). Diagnosis and management of asthma in adults: A review. JAMA, 318(3), 279-290.https://doi.org/10.1001/jama.2017.8372

National Asthma Education and Prevention Program (NAEPP). (2020). 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. The Journal of Allergy and Clinical Immunology, 146(6), 1217-1270.https://doi.org/10.1016/j.jaci.2020.10.003

Reddel, H. K., & Taylor, D. R. (2017). Asthma control: Still a challenge. The European Respiratory Journal, 50(3), 1701277.

Saito, N., & Kikuchi, T. (2016). An update on the pathophysiology and management of asthma. The Respiratory Medicine Case Reports, 19(12), 64-68.

Schrevens, L., Vansteenkiste, J., Deneffe, G., et al. (2004). Clinical-radiological presentation and outcome of surgically treated pulmonary carcinoid tumors: A long-term single institution experience. Lung Cancer, 43(1), 39-45.https://doi.org/10.1016/j.lungcan.2003.08.017

Turktas, H., Mungan, D., Uysal, M. A., et al. (2010). Determinants of asthma control in tertiary level in Turkey: A cross-sectional multicenter survey. Journal of Asthma, 47(5), 557-562.https://doi.org/10.3109/02770901003692777

Wenzel, S. E. (2012). Asthma phenotypes: The evolution from clinical to molecular approaches. Nature Medicine, 18(5), 716-725.https://doi.org/10.1038/nm.2678