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 Table of Contents  
CASE REPORT
Year : 2019  |  Volume : 7  |  Issue : 2  |  Page : 63-65

Successful treatment of bronchorrhea with gefitinib in a patient with bronchioloalveolar cell lung carcinoma


1 Department of Respiratory Medicine, Medical College, Kolkata, India
2 Department of Pediatric Medicine, Calcutta National Medical College, Kolkata, India
3 Department of Respiratory Medicine, Murshidabad Medical College, Murshidabad, West Bengal, India

Date of Web Publication20-Jun-2019

Correspondence Address:
Sibes Kumar Das
Souhardya Appartment, West BankimPally, Madhyamgram, Kolkata - 700129
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jacp.jacp_3_19

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  Abstract 

Bronchorrhea is defined as production of more than 100 mL watery sputum per day. Although found in several diseases and disorders, it is classically described in bronchioloalveolar cell lung carcinoma. It hampers the quality of life of the patient with lung cancer. Several treatment options are available for relief of this distressing symptom; however, none of them are effective in all cases. We herein report a case of a female with bronchioloalveolar cell lung carcinoma who presented with bronchorrhea. She showed dramatic symptomatic improvement with therapy with gefitinib.

Keywords: Bronchorrhea, bronchioloalveolar cell carcinoma, gefitinib


How to cite this article:
Das SK, Ghoshal B, Das A. Successful treatment of bronchorrhea with gefitinib in a patient with bronchioloalveolar cell lung carcinoma. J Assoc Chest Physicians 2019;7:63-5

How to cite this URL:
Das SK, Ghoshal B, Das A. Successful treatment of bronchorrhea with gefitinib in a patient with bronchioloalveolar cell lung carcinoma. J Assoc Chest Physicians [serial online] 2019 [cited 2019 Sep 15];7:63-5. Available from: http://www.jacpjournal.org/text.asp?2019/7/2/63/260589


  Introduction Top


Production of more than 100 mL of mucoid watery sputum per day is called bronchorrhea. This can result from several diseases and disorders like chronic bronchitis, asthma, pulmonary contusion, bronchiectasis, endobronchial tuberculosis, scorpion sting, organophosphorous poisoning, and others.[1] Few cases may also be idiopathic. However, adenocarcinoma of the lung especially the mucinous variety of bronchioloalveolar cell lung carcinoma (BACLC) is classically associated with this symptom. Bronchorrhea is present in 5% to 20% of patients with BACLC.[2] The volume of sputum of even more than 9 L/day has been reported.[3] This amount of sputum production results in breathlessness, exhaustion, anxiety, depression, and even respiratory failure due to flooding of the alveoli with secretions. Thus, it hampers the quality of life of a patient who is already suffering from a lethal disease. Concomitant presence of recurrent laryngeal nerve palsy and use of narcotic analgesics for relief of malignant pain further complicate the situation by preventing adequate cough reflex. Various modalities of treatment have been tried for symptomatic relief. They include palliative radiotherapy, anticholinergic drugs (hyoscine butyl bromide), intravenous methyl prednisolone, indomethacin inhalation, oral macrolides, beclomethasone inhalation, subcutaneous octreotide, etc.[4],[5] Recently, a very rapid and specific remedy of bronchorrhea in BACLC was described with tyrosine kinase inhibitors (TKIs) like gifitinib or erlotinib.[5],[6] Improvement of bronchorrhea is usually very prompt, often not more than within 1 week. We treated a 70-year-old female patient with bronchorrhea due to BACLC with gifitinib that produced remarkable decline in sputum production within few days.


  Case report Top


A 70-year-old female with a smoking history of 40 pack-years presented to a local physician with cough, copious mucoid expectoration, and progressive shortness of breath for last 2 months. Her blood examination revealed hemoglobin 10.3 g/dL, total leucocyte count 8000/mm3, neutrophils 67%, lymphocytes 30%, and eosinophils 3%. Her chest X-ray posteroanterior view showed areas of consolidation in right mid and lower zones [Figure 1]. With provisional diagnosis of community-acquired pneumonia of right middle lobe, she was put on intravenous injection of co-amoxiclav and oral azithromycin tablet for 10 days with no clinical improvement. She was referred to us for further evaluation. On interrogation, she disclosed that she was afebrile throughout her illness but gave history of significant weight loss and anorexia. There was no history of bone pain, headache, or yellow discoloration of urine. She was nondiabetic and normotensive with no significant past illness. She was producing 1 to 1.5 L of mucoid sputum per day. On examination, she was found to be afebrile, dyspnoeic with pulse rate 100/min, respiratory rate 28/min, blood pressure 140/80 mmHg, axillary temperature 37°C, and SpO2 94% at room air. Chest examination revealed bronchial breath sound, increased vocal resonance, and fine crackles in right infraaxillary and mammary area. Examination of other systems revealed no abnormality. Chest X-ray posteroanterior view was repeated that showed identical changes as the previous X-ray. Complete hemogram revealed low hemoglobin level (9.5 g/dL) with normal total and differential leukocyte count. Blood biochemistry was within normal limits. Sputum smear for gram stain, Ziehl–Neelsen stain, and papanicolaou stain were negative. Elisa test for HIV 1 and 2 was nonreactive. Ultrasonography of whole abdomen revealed no abnormality. Contrast-enhanced computed tomography scan of thorax showed areas of consolidation and ground glass opacities in right middle and lower lobes [Figure 2]. Tru-cut biopsy of the right lung opacity revealed histological picture of BACLC [Figure 3]. Fiber optic bronchoscopy was not done as she declined to give consent for the procedure. Epithelial growth factor receptor gene mutation study was not done due to financial constraints. She was diagnosed as a case of bronchioloalveolar cell carcinoma of the right lung. She was put on gefitinib tablet 250 mg daily for relief of bronchorrhea. The volume of her sputum started to decrease by third day and went on decreasing till the amount was less than 20 mL/day by day 12. She was put on palliative chemotherapy with cisplatin and gemcitabane. Her condition stabilized after fourth cycle of chemotherapy.
Figure 1 Chest X-ray posteroanterior view showing areas of consolidation in right mid and lower zones.

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Figure 2 Contrast-enhanced computed tomography scan of thorax showing areas of consolidation and ground glass opacities in right middle and lower lobes.

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Figure 3 Tru-cut biopsy of the right lung opacity revealed histological picture of bronchioloalveolar cell lung carcinoma.RESPIRATORY

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  Discussion Top


Adenocarcinoma of the lung may produce considerable amount of mucus as the malignant change precisely affects the cells responsible for mucus synthesis and excretion.[4] In BACLC, both increased secretion of bronchial mucus glands and increased serum transudation through the tumor cell have been proposed as possible mechanisms for bronchorrhea. It is more common in mucinous variety of BACLC. Several treatment options are available for symptomatic relief. Palliative radiotherapy can reduce the volume of sputum production but often produce cumbersome local and systemic side effects. Anticholinergic drugs are not only ineffective but also carries the risk of xerostomy. Corticosteroid may reduce the secretion by inhibiting the genes from encoding cycloxygenase-2. Indomethacin also inhibits cycloxygenase pathway leading to reduction of transepithelial chloride secretion. Macrolides are specific inhibitors of glycoprotein secretion leading to less synthesis of mucin protein. Octreotide inhibits secretine, responsible for shift of electrolytes across the membranes. Recently, Epithelial growth factor receptor (EFTR) TKI like gefitinib or elrotinib has shown promising results in symptomatic treatment of bronchorrhea. Mucins are highly glycosylated oligometric glycoproteins secreted by goblet cells of airway epithelium and mucus cells of submucosal glands. Out of the 19 mucin genes cloned so far, MUC5AC and MUC5B are found in goblet cell and mucus cells, respectively. Most extensively studied pathway for transcriptional regulation of mucus gene expression is the epithelial growth factor receptor (EGFR) pathway. Stimulation of EFTR by its ligands like epidermal growth factor and transforming growth factor-α causes MUC5AC expression in airway epithelial cells.[7] EGFR expression and activation also cause goblet cell metaplasia from Clara cells. Gefitinib may inhibit MUC5AC synthesis through mitogen-activated protein kinase and protein kinase B (AKT) pathway.[8] The receptor tyrosine kinase EGFR is mutated in approximately 10% of whites and 40% of East Asian patients with nonsmall cell lung cancer leading to constitutive activation of this growth factor receptor. Interruption of this pathway with TKIs like gefitinib or erlotinib is an example of successful therapeutic approach in the treatment of nonsmall cell lung cancer especially of adenocarcinoma histology. Tumor response with gefitinib is usually associated with relief of tumor-related symptoms like bronchorrhea. However, improvement of bronchorrhea has also been reported with TKI in BACLC without EGFR mutation and without tumor response.[9] This is because the mechanism of reduction of bronchorrhea is independent of antiproliferative effect of these drugs.


  Conclusion Top


Bronchorrhea in BACLC should be initially treated with erlotinib or gefitinib for at least 1 week in all patients irrespective of EGFR mutation status or tumor response. Other therapies may be opted as an alternative when bronchorrhea does not improve by 1 week or is resistant to therapy or in case of relapse while on TKI.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Seaton A. Clinical aspects. In: Seaton A, Seaton D, Leitch AG, editors. Crofton and Doglas’s Respiratory Diseases, vol. 1, 5th ed. London: Blackwell Science; 2000. pp. 102-18.  Back to cited text no. 1
    
2.
Rubiales AS, Berezo JA, Torres MA. Erlotinib or gefitinib as first-choice therapy for bronchorrhea on bronchioloalveolar carcinoma. J Pain Symptom Manag 2014;47:e7-9.  Back to cited text no. 2
    
3.
Hidaka N, Nagao K. Bronchioloalveolar carcinoma accompanied by severe bronchorrhea. Chest 1996;110:281-2.  Back to cited text no. 3
    
4.
Zylicz Z. The challenge of bronchorrhoea in advanced cancer − a case report with review of literature. Adv Pall Med 2010;9:9-12.  Back to cited text no. 4
    
5.
Thotathil Z, Long J. Erlotinib effective against refractory bronchorrhea from advanced non-small cell lung cancer. J Thorac Oncol 2007;2:881-2.  Back to cited text no. 5
    
6.
Takao M, Inoue K, Watanabe F, Onoda K, Shimono T, Shimpo H et al. Successful treatment of persistent bronchorrhea by gefitinib in a case with recurrent bronchioloalveolar carcinoma: a case report. World J Surg Oncol 2003;1:8.  Back to cited text no. 6
    
7.
Takeyama K, Dabbagh K, Lee HM. Epidermal growth factor system regulates mucin production in airways. Proc Natl Acad Sci USA 1999;96:3081-6.  Back to cited text no. 7
    
8.
Kitazaki K, Soda H, Dol S, Nakano H, Nakamura Y, Khno S. Gefitinib inhibits MUC5AC mucin-secreting non small cell lung cancer cells. Lung Cancer 2005;50:19-24.  Back to cited text no. 8
    
9.
Popat N, Raghavan N, Mclvor RA. Severe bronchorrhea in a patient with bronchioloalveolar carcinoma. Chest 2012;141:513-4.  Back to cited text no. 9
    


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  [Figure 1], [Figure 2], [Figure 3]



 

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