Nebulised N-Acetylcysteine for Unresponsive Bronchial Obstruction in Allergic Brochopulmonary Aspergillosis: A Case Series and Review of the Literature
Abstract
:1. Introduction
2. Methods
3. Results
4. Literature Review
4.1. N-Acetylcysteine—The Archetypal Classical Mucolytic
4.2. Pharmacokinetics of N-Acetylcysteine
4.3. N-Acetylcysteine Products on the Market
4.4. Nebulized versus Oral N-Acetylcysteine
4.5. Asthma with Hypersecretion of Mucus—Use of N-Acetylcysteine Down A Bronchoscope
4.6. Intravenous N-Acetylcysteine
4.7. Mucoid Impaction—What Is It and Does N-Acetylcysteine Help?
4.8. Allergic Bronchopulmonary Aspergillosis and Hyperattenuated Allergic Mucin
5. Conclusions
Funding
Conflicts of Interest
References
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Sex | Age | Diagnosis | Co-Morbidities | Duration of NAC Use | Outcome | FEV1 Pre/Post (Liters) | Any Other Relevant Clinical Information? |
---|---|---|---|---|---|---|---|
Female | 50 | CPA, ABPA | Asthma, bronchiectasis, adrenal insufficiency, and previous left upper lobectomy for bronchiectasis | 14 days | Discontinued. No change in symptoms | 1.67/1.53 | Trialed in order to try and avoid bronchoscopy. She was already receiving daily physiotherapy after 8 mL of 7% saline via nebulizer. The challenge with NAC was followed by intermittent positive pressure breathing therapy, 8 mL 7% saline and active cycle of the breathing technique |
Male | 63 | ABPA | Asthma, coeliac disease, sinusitis, hypertension vitamin D deficiency, liver cysts, and hyperaldosteronism | 1 | Failed initial challenge due to increased breathlessness. However, he was able to expectorate freely and provided a sputum sample which he hadn’t managed to do previously | 2.25/1.96 | Had not taken his usual dose of Fostair/salbutamol that morning. He was noted to be wheezy pre-challenge. Post NAC challenge, he was given 2 puffs of salbutamol via a metered dose inhaler. |
Female | 59 | ABPA | Asthma, vocal cord dysfunction, bronchiectasis, and tracheal stenosis | Long term since 2/10/2014 | Discontinued. No change in symptoms | Not performed-tracheostomy patient. No change on auscultation/pulse oximetry (98%)/heart rate | Prior to challenge that had already self-suctioned 6 times that morning. Already nebulizing budesonide, salbutamol, 7% saline and colistin |
Male | 47 | ABPA | Right upper lobectomy | 1 week | Discontinued. No change in symptoms | 4.15/4.10 | Never tried 7% saline via a nebulizer |
Female | 57 | Aspergillus terreus and Trichoderma bronchitis | Hypothyroidism, migraine, and bronchiectasis | 8 months. A clinical decision was made to stop NAC as she felt much better post bronchoscopy | Well tolerated, increased expectoration of phlegm | 1.99/1.89 | Already on 7% saline via nebulizer. Underwent bronchoscopy with lavage 8 months after commencing NAC |
Female | 83 | ABPA Recurrent left lower lobe collapse | Hypertension, osteoarthritis, glaucoma, and nasal disease of uncertain aetiology | 7 months | Tolerated NAC. Eventually discontinued as she derived greater benefit from 7% saline nebs | NAC appeared to aggravate her cough. No further lobar collapse recorded |
Drug | Device | Indication | Proposed Mechanism of Action | Notes |
---|---|---|---|---|
Expectorants | ||||
Hypertonic saline 7% | Nebulizer | Cystic fibrosis, and bronchiectasis | Increases the amount of sodium and chloride in airway surface liquid, thereby increasing the osmotic gradient and rehydrating the mucus layer [5,7] | Improves lung function and quality of life in bronchiectasis [8]. Should not be given via a vibrating mesh nebulizer. Improves mucus clearance, airflow, and reduces rates of exacerbation among patients with cystic fibrosis [4,9]. |
Classical mucolytics | ||||
NAC (Mucomyst®) | Nebulizer | ABPA | Severs disulfide bonds that link mucin monomers to polymers, and solubilizes sputum antioxidant and anti-inflammatory | No evidence for use in any lung disease. |
S-carboxymethylcysteine (carbocysteine) | Oral | COPD, and cystic fibrosis | Increases concentrations of sialomucins and reduces that of fucomucins, acts as a free radical scavenger [10], and has antioxidant and anti-inflammatory properties | Reduces measured sputum viscosity [11,12]. |
Dry powder mannitol (Bronchitol®) | Dry powder inhaler | Cystic fibrosis, bronchiectasis, and COPD | Increases mucus secretion | Nonabsorbable. Associated with bronchoconstriction and cough when used in children with cystic fibrosis. |
Peptide mucolytics | ||||
Dornase alfa (Pulmozyme®) | Nebulizer | Cystic fibrosis | Hydrolyzes DNA polymer and reduces DNA length | Hydrolyzes DNA, improves lung function, and decreases the frequency of exacerbation [13,14]. |
Nondestructive mucolytics | ||||
Unfractionated heparin (UFH) | Nebulizer | COPD, and cystic fibrosis | Modifies ionic interactions and the intermolecular hydrogen bonds between mucin molecules, and untangles the charged oligosaccharide side chains of mucin | UFH reduces the elasticity and yield stress in the samples from cystic fibrosis patients [15]. |
Low molecular weight dextran (DCF 987) | Nebulizer | COPD | Disrupts the polyionic oligosaccharide mucin network and increases secretion hydration | Proven lung safety in animal studies [16,17]. |
Brand | Preparation | Administration | Side Effects |
---|---|---|---|
Mucomyst® by Bristol-Myers Squibb | Sterile unpreserved solutions (not for injection) of 20% (Mucomyst-20) or 10% (Mucomyst-10) acetylcysteine, with edetate disodium in purified water. Sodium hydroxide is added to adjust pH to 7. | Nebulization using face mask, mouth piece, tracheostomy, tent or croupette, direct introduction into a segment of the bronchopulmonary tree via a plastic catheter, and can also be given via a percutaneous intratracheal catheter and during bronchoscopy. | Stomatitis, nausea, vomiting, fever, rhinorrhea, drowsiness, clamminess, and bronchoconstriction. Acquired sensitization to NAC may rarely occur. |
Fluimucil by Zambon | Capsules 200 mg, effervescent tablets 600 mg, paediatric sachet 100 mg, granules 200 mg, dry syrup 100 mg/5 mL, and injection suspension (ampoule) 300 mg/3 mL | Oral and aerosol administration | Capsule/granule/dry syrup: heartburn, nausea, vomiting, diarrhoea, stomatitis, dizziness, tinnitus, allergic and reduced blood pressure. IV: hypersensitivity reactions, rhinorrhea, stomatitis, nausea and vomiting. |
Acetadote® injection by Cumberland Pharmaceuticals Inc. Nashville, TN 37203 | 20% solution in 30 mL (200 mg/mL) single-dose glass vials, preservative-free for IV administration. | For IV administration | Anaphylactoid reaction due to pyrogens, flushing, oedema, urticaria, pruritus, nausea, pharyngitis, rhinorrhea |
Cetylev® tablets by Alpex Pharma SA | Effervescent tablets 500 mg or 2.5 grams of NAC. | Oral administration | Nausea, vomiting, other gastrointestinal symptoms, and rash with or without fever. |
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Otu, A.; Langridge, P.; Denning, D.W. Nebulised N-Acetylcysteine for Unresponsive Bronchial Obstruction in Allergic Brochopulmonary Aspergillosis: A Case Series and Review of the Literature. J. Fungi 2018, 4, 117. https://doi.org/10.3390/jof4040117
Otu A, Langridge P, Denning DW. Nebulised N-Acetylcysteine for Unresponsive Bronchial Obstruction in Allergic Brochopulmonary Aspergillosis: A Case Series and Review of the Literature. Journal of Fungi. 2018; 4(4):117. https://doi.org/10.3390/jof4040117
Chicago/Turabian StyleOtu, Akaninyene, Philip Langridge, and David W. Denning. 2018. "Nebulised N-Acetylcysteine for Unresponsive Bronchial Obstruction in Allergic Brochopulmonary Aspergillosis: A Case Series and Review of the Literature" Journal of Fungi 4, no. 4: 117. https://doi.org/10.3390/jof4040117