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Division the Hematology/Oncology and also Palliative Care, department of internal Medicine (M.P., L.J.L.); and division of Pulmonary and critical Care (R.W.S.), Virginia republic University, Richmond, Virginia, USA
Address correspondence to: Meera Pahuja, MD, MSc, room of inner Medicine, Virginia republic University, 1101 eastern Marshall Street, P.O. Crate 980230, Richmond, VA 23298, USA. Ude.ucv-hvcm

Octreotide, a man-made analogue that the hormone somatostatin, is primarily used in palliative medicine due to the fact that of the antisecretory effect and also has been presented to be efficient in the administration of bowel obstruction, nausea, and diarrhea. Octreotide also has been efficiently used because that the monitoring of bronchorrhea in both inpatient and outpatient settings. Us report the instance of a 47-year-old female with a history of bronchioloalveolar cell carcinoma who copious bronchial secretions were managed with octreotide. Octreotide must be further evaluated together a first-line treatment for bronchorrhea.

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Keywords: Bronchorrhea, octreotide, bronchioloalveolar carcinoma

Introduction

Bronchorrhea is arbitrarily identified as the production of an ext than 100 mL that watery sputum per day.1 that is typically associated with malignancy, particularly bronchioloalveolar cell carcinoma (BAC) and also pulmonary metastases. The BAC is a subtype of pulmonary adenocarcinoma, i beg your pardon is additional subdivided into mucinous, nonmucinous, and an intermediate form. The mucinous form arises indigenous mucinous metaplasia of bronchiolar cells and is connected with mucosecretion. Rates of BAC space increasing and it accounts for 3–9% of brand-new lung cancer diagnoses, of i m sorry 20–25% space the mucinous form.2 although uncommon, bronchorrhea also is linked with nonmalignant processes such as chronic bronchitis, asthma, tuberculosis, and scorpion stings.

Excess sputum production in patients with BAC is assumed to be brought about by a few different mechanisms. First, inflammatory stimuli space thought to cause hypersecretion that mucous glycoprotein. Takeyama et al.3 suggested linkage to an epidermal expansion factor receptor (EGFR) pathway in i m sorry stimulation that EGFR causes MUC5AC expression in airway epithelial cell in vivo and also in vitro. The MUC5AC is a significant component of the rubber matrix creating a family members of mucins in the airways.4 Bronchorrhea likewise is believed to be brought about by enhanced trans-epithelial chloride secretion, which consequently is linked with the excretion the water. Finally, the is assumed to be related to extreme transudation the plasma commodities into airways.5 The true incidence of bronchorrhea in patients v BAC is no known; but one review found that it occurs in 6% of the cases.6

Despite its rare occurrence, as soon as bronchorrhea go occur, that causes far-reaching morbidity for patients and may lead to too much coughing, dyspnea, and also exhaustion. In addition to the physics symptoms, the profuse sputum manufacturing can cause difficulties v social integration. Also, there have actually been reports of boosted sputum production causing electrolyte imbalances, dehydration, and also even respiratory failure.7


Case Description

We report right here the effective treatment of bronchorrhea making use of octreotide in a 47-year-old female through BAC. The patient presented to pulmonary clinic in July 2011 through a chief complaint of “coughing increase too much sputum” for two months and producing about 1 l of sputum per day. She additionally noted significant dyspnea, chest pressure, and pain connected with the chronic cough. She was diagnosed through BAC in 2004 and initially had actually a left lung lobectomy. She underwent a right lung wedge resection in 2006, and likewise received radiation and also chemotherapy.

Despite treatment, the cancer progressed and she provided increasing watery sputum production beginning in 2009. In ~ presentation come pulmonary clinic, her symptoms had significantly impaired her quality of life. She had been managed with levalbuterol, glycopyrrolate, guaifenesin, orally inhaled tiotropium, salmeterol, opioids, and also prednisone, there is no reduction in sputum quantity. A computed tomography scan of the chest on join showed marked progression of condition in the parenchyma of both lungs, with raising left lung consolidations, multiple cavitating pulmonary nodules, and new diffuse consolidations the the ideal lung.

Case reports imply that subcutaneous (SC) octreotide has actually been used properly to treat bronchorrhea; however, the patient to be fearful that SC injections. She was admitted come the inpatient palliative care unit because that a trial of intravenous (IV) octreotide at 12.5 μg/hour. After 24 hours, her secretions had diminished to 150 mL/day; and also by 72 hours, she had created a total of 500 mL of sputum. Top top hospital day 4, the octreotide to be discontinued and her secretions remained minimal. She to be discharged v a setup for SC management of octreotide; however, the patient opted rather to receive day-to-day IV infusions of octreotide in the outpatient clinic.

Five job after discharge, she detailed that her sputum production boosted to unacceptable levels within 12 hrs of the IV infusion. One main after discharge, she to be readmitted come the inpatient palliative care unit because that the monitoring of bronchorrhea and started again on IV octreotide through reduction in her sputum to 100 mL/day. She to be discharged on 200 μg octreotide administered through SC path twice a day.

When the patient was evaluated in the outpatient clinic four weeks later, the was provided that she secretions decreased with SC management of octreotide, and her symptom of dyspnea, chest pressure, and also cough had actually improved. That note, there to be no other medications that were changed to account because that the significant improvement in symptoms.


Comment

This case describes the management of a rare yet really burdensome symptom frequently connected with BAC. Regulating the symptoms concerned bronchorrhea deserve to be difficult, return there room a couple of case reports in the literature saying the success of miscellaneous treatments. Macrolide antibiotics and also steroids have actually been shown to reduce sputum volume manufacturing in patients through BAC second to the anti-inflammatory impact of this drugs, i beg your pardon act as immunomodulators and also reduce mucin gene expression. Hiratsuka et al.8 found that clarithromycin treatment in conjunction v inhaled beclomethasone diminished sputum volume from 900 to 300 mL a job in a patient through bronchorrhea secondary to BAC. Furthermore, they found that after preventing the clarithromycin and continuing inhaled beclomethasone alone, the bronchorrhea was controlled for four more months. There likewise are situation reports of effective treatment the bronchorrhea v corticosteroids alone in patients through BAC. Nakajima et al.9 described the successful treatment that bronchorrhea in a patient with BAC v high-dose pulse methylprednisolone 1000 mg/day complied with by dental prednisolone 60 mg/day. The patient’s sputum volume was regulated at 10 mL/day after four weeks the treatment.

There have been instance reports about the effective use the inhaled indomethacin for the management of bronchorrhea. Increased transepithelial chloride transport can be promoted by prostaglandins, which are inhibited by indomethacin. Inhaled indomethacin to be reported to be reliable for severe refractory bronchorrhea in two patients through BAC, not only reducing sputum volume but likewise improving top quality of life.10

There likewise have been promising reports that the use of gefitinib in the administration of bronchorrhea. Gefitnib is an dental selective EGFR-tyrosine kinase inhibitor. That is assumed that EGFR expression and also activation causes goblet cell metaplasia indigenous Clara cells and also mucus hypersecretion in the airway.11 Takao et al.12 reported effective treatment of bronchorrhea in a 63-year-old female through BAC after 2 weeks that gefitinib therapy. She was preserved on gefitinib for nine month without symptoms and also without radiologic evidence of recurrence the disease. A recent instance report through Popat et al.5 also showed the successful use the gefitinib in a 46-year-old man with BAC despite his an adverse EGFR mutation status. The authors indicate that successful use that gefitinib because that bronchorrhea is elevation of its antiproliferative effect and likely secondary to the function of EGFR in regulation mucin production.5

There likewise are case reports of therapy of bronchorrhea v octreotide in patients v BAC. Hudson et al.13 explained the successful use that octreotide with SC route to manage the symptom of bronchorrhea in a 74-year-old female v BAC. The patient to be producing an ext than 1 l of sputum every day; and also after two days the octreotide therapy, sputum manufacturing subsided completely.

Octreotide is a artificial analogue of the hormone somatostatin; and although the exact mechanism of activity is unknown, that is thought to act on the same receptors together somatostatin. Octreotide inhibits the secretion of numerous hormones including gastrin, cholecystokinin, glucagon, development hormone, insulin, secretin, pancreatic polypeptide, thyroid-stimulating hormone, and also vasoactive minister peptide. Therefore antisecretoy effect, octreotide reduces cradle motility, inhibits gall-bladder contraction, reduces cheap of fluids through the intestine and also pancreas, and has even been displayed to have actually an analgesic effect.14

Octreotide has long been supplied by palliative treatment practitioners to manage symptoms, consisting of malignant bowel obstruction,15 ascites,16 nausea,17 and also gastrointestinal hemorrhage.18 It additionally has been provided to manage excessive secretions concerned fistulae.19 as a result of that antisecretory effect, octreotide is a potent antidiarrheal agent and also has been supplied to regulate diarrhea concerned carcinoid syndrome20 and human immunodeficiency virus–related diarrhea.21

Common side results of octreotide encompass headache; gastrointestinal reactions consisting of cramps, nausea, vomiting, diarrhea, and also constipation; gallstones; hyperglycemia; hypoglycemia; and transient injection site reactions. Octreotide likewise is provided among drugs that can expand the QT interval; however, studies space inconclusive regarding whether the prolonged QT interval is the an outcome of octreotide or straight related to the offending illness that forced octreotide management, such as acromegaly.22 that is crucial to note that the patience in our report did not suffer any type of known side results related to the octreotide throughout both the IV and also SC management of the drug. She did have actually pain concerned the SC injections; however, no injection website reaction was noted.

It is believed that bronchorrhea is caused by raised transepithelial chloride cheap in the lungs. Octreotide lowers plasma levels of the hormone secretin and also there space secretin receptors current on the human lung.12 Secretin is a potent stimulant of electrolyte and also water movement, and it has been argued that inhibiting secretin reduce chloride and water efflux indigenous bronchial epithelial cells, thereby reducing sputum production.13

As prove in this situation report, over there are countless ways to administer octreotide. In enhancement to the IV and SC routes, there likewise is one intramuscular depot injection. One intramuscular depot injection may regulate symptoms because that up to four weeks. However, the intramuscular depot injection can be price prohibitive. In one large U.S. Academic medical center, the price of a 20 mg depot injection is $2319, versus IV and also SC administration, each of which only cost about $10 per day. Offered the added cost the administering octreotide daily by the IV or SC routes, more studies room warranted to establish if the is cost-effective to use the intramuscular depot injection in patient who have actually known improvement of symptoms with octreotide. In addition to the costs, one have to take into account the included burden come patients that is associated with day-to-day IV or SC administration.

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This situation report highlights the use of octreotide to successfully regulate bronchorrhea in miscellaneous health care settings, such as inpatient palliative treatment units, outpatient clinics, and also home-based therapy. The report also touches ~ above the various administration modalities the octreotide that have the right to be offered for symptom management throughout these settings. Octreotide has been successfully used because that the administration of bronchorrhea and should be more studied and considered as first-line treatment.