Sputum, Gotta Love The Stuff!

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1 Sputum, Gotta Love The Stuff! Douglas S. Gardenhire, EdD, RRT-NPS, FAARC Associate Professor and Chairman Department of Respiratory Therapy Georgia State University

2 Objectives Differentiate mucus from sputum. Discuss factors associated with abnormal mucus production. Discuss diseases associated with abnormal mucus production. Discuss mucoactive agents. Discuss mucoactive treatments.

3 Overview What is mucus doing for me? Source Factors associated with mucus Mucus and disease vs. Sputum Physical Properties Mucoactive Agents Mucoactive Treatments

4 Mucociliary Escalator Major Defense mechanism Failure Obstruction Thickened adhesive secretions Slowed with disease

5 Mucus.Where and Why Airways Gastrointestinal tract Genital tract Protective Lubricating Waterproofing

6 Source of Airway Secretions Mucus Gel Layer Moved by cilia towards larynx Sol Layer Watery layer below gel layer Produced by Surface epithelial cells Goblet cells Submucosal glands

7 From Gardenhire, D. (2016). Rau s Respiratory Care Pharmacology, Elsevier

8 From Gardenhire, D. (2016). Rau s Respiratory Care Pharmacology, Elsevier

9 Surface Epithelial Cells Surface of Trachea/bronchi Ciliated cells Goblet cells More than 6000 goblet cells per square mm of airway Responds only to irritants Submucosal Glands Produces most of mucus in airway Parasympathetic control Cholinergic Stimulation Possible Sympathetic Innervation

10 From Gardenhire, D. (2016). Rau s Respiratory Care Pharmacology, Elsevier

11 Factors Affecting Mucociliary Transport COPD CF Dry airway (dry gas from MV) Narcotics Suctioning; Trach Cigarette smoke Pollutants Hyperoxia and Hypoxia

12 Food Intake and Mucus Production Does milk or dairy increase mucus? NO No reason to withhold milk from patients with colds, RTI, or chronic disease Pinnock CB, etal Am Rev Respir Dis 141:352, 1990

13 Composition of Mucus 95% water 5% protein

14 Mucus and Disease Chronic Bronchitis Asthma Bronchorrhea Plastic Brochitis Cystic Fibrosis

15 Rogers D, Mucoactive agents for airway mucus hypersecretory diseases. Respir Care 2007;52(9):1181

16 Chronic Bronchitis Clinically, daily X 3 mon; X 2yrs Hyperplasia goblet cells Goblet cells increase in number Submucosal glands hypertrophy Tobacco smoke; # 1 irritation factor Cause; mucus hypersecretion Associated with rapid decline in lung function Rubin BK, etal. Clin Pulm Med 5:1, 1998; Vestbo J, etal Am J Respir Crit Care Med 153:1530, 1996.

17 Asthma Hypersecretion can occur during exacerbation 80% of all patient report increased sputum Beta agonists on board- Problem? Beta agonists cause hypersecreation IV/Continuous nebulization Fatality? Turner-Warwick M. etal. Postgrad Med J 63(suppl 1):79, Rubin BK, Pediatr Pulmonol Suppl 23:88, Webber SE, etal. Agents Actions 22:82, 1987.

18 Bronchorrhea Clinically 100 ml of watery sputum daily Occurs in about 9% of asthmatics Treat with corticosteroids and/or antibiotics Shimura S, etal. Chest 94:1211, 1988; Marom ZM, etal. J Allergy Clin Immunol 87:1050, 1991.

19 Plastic Bronchitis Rare, Clinically, rigid airway casts Patients may cough up casts of the TB Tree May be toothpaste or pudding-like Madsen P, Shah SA, Rubin BK: Paediatr Respir Rev 6:292, 2005.

20 Cystic Fibrosis Chronic hereditary disease Impaired function of CFTR protein Chronic airway infection with Pseudomonas and other gram bacteria Chronic airway inflammation NO hypersecretion of airway Very little to no mucus in sputum Airway filled with PUS Similar sputum to bronchiectasis Bush A, Payne D, Pike S, Jenkins G, Henke MO, Rubin BK: Chest 129:118, 2006.

21 Physical Properties of Mucus Mucus (low viscosity, high elasticity ) Sputum (viscosity increases) From Gardenhire, D. (2016)Rau s Respiratoy Care Pharmacology, Elsevier

22 Mucoactive Agents

N-ACETYL L-CYSTEINE (NAC) Reduce hepatic injury with acetaminophen overdose Long history of use No evidence of clinical efficacy Inhaled NAC can cause bronchospasm Breaks down mucus, not sputum

23 N-ACETYL L-CYSTEINE (NAC) Reduce hepatic injury with acetaminophen overdose Long history of use No evidence of clinical efficacy Inhaled NAC can cause bronchospasm Breaks down mucus, not sputum Difference between mucus & sputum Decramer M, Rutten-van Molken M, Dekhuijzen PN, Troosters T, van Herwaarden C, Pellegrino R et al.: Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trial, Lancet 365 (9470): , 2005.

24 Rogers D, Mucoactive agents for airway mucus hypersecretory diseases. Respir Care 2007;52(9):1181

Dornase Alfa (Pulmozyme) Reduces DNA and F-actin polymers Shak s, etal Proc Natl Acad Sci USA 98:9188, 1990 No efficacy in acute exacerbations No efficacy in

25 Dornase Alfa (Pulmozyme) Reduces DNA and F-actin polymers Shak s, etal Proc Natl Acad Sci USA 98:9188, 1990 No efficacy in acute exacerbations No efficacy in non-cf bronchietasis Wilmott RW, etal Am J Respir Crit Care Med 153:1914, 1996 May decrease effectiveness of aminoglycosides Ramsey BW, etal Pediatr Pulmonol 17:404, 1994

26 Courtesy Bruce K. Rubin, From Gardenhire D, (2016) Rau s Respiratory Care Pharmacology, Elsevier

27 Expectorants

28 Iodide Containing Agents Supersaturated Potassium Iodide (SSKI) Stimulate airway fluid secretion Has failed to makes changes to PFT or sputum Rubin B, etal Chest 109:348, 1996

29 Sodium Bicarbonate Tracheal instillation or Inhalation 2% concentration Increases bronchial ph Breaks bonds, decreasing viscosity and elasticity Not clinically shown to increase mucus clearance From Gardenhire D, (2008) Rau s Respiratory Care Pharmacology, Mosby

Increases mucus production Not been demonstrated to

30 Guaifenesin Can be toxic to cilia if directly applied Works by stimulation of submucosal gland Increases mucus production Not been demonstrated to be effective, clinically Rubin BK, etal. Chest 116:195, 1999

31 Mucus Why Protective Lubricating Waterproofing

32 Oligosaccharides Oligosaccharides side chains make up 80% of mucus Aerosolized low wt molecular heparin Used in treatment of asthma Interferes with antigen-receptor binding Disrupting H+ bond Same thought for use of aerosolized mannitol and dextran Ahmed T, etal. N Engl J Med 329:90, 1993

34 Mucokinetics

35 Bronchodilators Beta-agonists Produce mucus, can cause problems Mucus trapping, fatal asthma Work best by increasing airflow Newhouse, MT Euro J Respir Dis Suppl 124:151, 1983

36 Other

37 Hyperosmolar Saline 6% saline increased CF patients PFT Shown to improve PFTs in CF and non-cf bronchiectasis patients. Daviskas E. etal. Respirology 10:46, 2005 Mannitol has been effective in non-cf bronchiectasis patients Wills P, etal. Cochrane Database Syst Rev 3: CD001506, 2006 Not as effective as dornase alfa in CF Suri R, etal. Lancet 358:1316, 2001 Due to cough induction, aerosolized antibiotic therapy must be last!

38 Hypertonic Saline 7% hypertonic solution Commonly used in CF Believed to increase FEV1 by decreasing mucus Pulmosal FDA-cleared, buffered with sodium bicarbonate to a ph of 7.4. Others are acidic ph of 4.5 to 7.0 Pseudomonas aeruginosa has an affinity to colonize in an acidic ph of ~6.0.

39 PulmoSal vs. Hypertonic Saline

40 Mucoactive Therapy

41 Physiotherapy and Breathing Gravity Best if added to conventional CPT Mucus blanket can resist gravity alone GERD is a major problem Thomas J, etal. Am J Respir Crit Care Med 151:846, 1995 Breathing techniques Active cycle breathing (ACB) Diaphragmatic breathing with deep breaths Forced expiratory technique (FET) Huff cough with glottis open Hansani A, etal. Chest 105:1420, 1994 Exercise Increases sputum production Bilton, D, etal. Thorax 44:859, 1989

42 Insufflation-Exsufflation Stimulates cough with + and pressure Bach JR, Chest 105:1538, 1994

43 Positive Airway Pressure PEP Pursed lip breathing More effective than IS or IPPB Ricksten, SE, etal. Chest 89:774, 1986

Oscillation of the Airway Flutter Little

44 Oscillation of the Airway Flutter Little research done 3 times more sputum in CF than cough or PD Konstan MW, etal. J Pediatr 124:689, 1994 Not confirmed or effective Homnick DN, etal. Chest 114:993, 1998 App EM, etal. Chest 114:171, 1998 Acapella Lung Flute Effective for sputum sampling Quake Generates vibrations on inhalation and exhalation

45 Lung Flute

46 Chest Wall Oscillation Vest Effective in CF Kluf J, etal. Pediatr Pulmonol 22:271, 1996 Not established in non-cf patients

47 HFCWO

48 Summary Difference between Mucus and Sputum Sputum becomes more viscid Mild does not thicken secretions A number of different solution available CPT is a gold standard Use exercise NAC does not work on pulmonary sputum Pulmozyme is only used for CF

49 Questions, Comments, Happy Thoughts?

Chapter 9. Mucus-controlling Drug Therapy. Mosby items and derived items 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc.

Chapter 9. Mucus-controlling Drug Therapy. Mosby items and derived items 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc. Chapter 9 Mucus-controlling Drug Therapy Drug Control of Mucus: A Perspective Mucociliary escalator is a major defense system Failure may result in mechanical obstruction of the airway Properties of mucus