![Cough - Acute
• Most common causes
– Common cold [viral]
– Acute bacterial sinusitis
– Pertussis
– Exacerbation of COPD
– Allergic rhinitis
– Rhinitis secondary to environmental irritants](https://image.slidesharecdn.com/cough-130202224209-phpapp01/85/Cough-5-320.jpg)
More Related Content
Cough
- 1. Cough – TheChallenge of treatment Dr. B. K. Iyer
- 2.
- 3. How long? • Sudden - ? Foreign body • Days - infection • Weeks – bronchitis/pneumonia/TB/cancer • Months/years – chronic bronchitis/reflux • Variable - asthma
- 4. Cough - History Cough Acute Subacute Chronic Less than 3 Less than 3 3 to 8 weeks 3 to 8 weeks More than More than weeks weeks 3 weeks 3 weeks Richard Irwin, NEJM, Volume 343, Dec 7, 2000
- 5. Cough - Acute •Most common causes – Common cold [viral] – Acute bacterial sinusitis – Pertussis – Exacerbation of COPD – Allergic rhinitis – Rhinitis secondary to environmental irritants
- 6. Cough – ViralInfection • Upper respiratory viral infections are the most common cause of cough – 83% within first 48 hours – 26% on day 14 • Arises from the stimulation of the cough reflex in upper airway by postnasal drip and/or clearing of the throat
- 7. Cough – ViralInfection • Signs and symptoms include: rhinorrhea, sneezing, nasal obstruction, post nasal drip, irritation of the throat, +/- fever and normal chest exam – Diagnostic testing is not indicated in a immunocompetent patient as there is a very low yield — over 97% of CXR are normal
- 8. Cough - Acute •Remember: – Think bacterial bronchitis & use antibiotics if exacerbation of COPD with worsening SOB or wheezing is present – Cough and vomiting is suggestive of Bordetella pertussis – Bacterial sinusitis can present like a viral rhinitis but use antibiotics only two of the following are present: • Maxillary toothache • Purulent nasal discharge, discolored nasal discharge • Abnormal transillumination of any sinus
- 9. Cough - Acute •In elderly, classic signs and symptoms may be minimal, so consider – Pneumonia – CHF – Asthma – Aspiration
- 10. Cough - Subacute •Most common etiologies 1. Post-infectious cough • Begins with respiratory tract infection • NOT pneumonia • Ultimately resolves without treatment • Results from PND or clearing of throat • With or without bronchial hyper-responsiveness 1. Bacterial sinusitis 2. Asthma
- 11. Postinfectious Cough - Treatment • Begin with treatment similar to the common cold • If wheezing – use bronchodilators – This does not make the diagnosis of asthma • If not resolved in one week • Nasal decongestant for 5 days • Antibiotics till total disappearance of cough
- 12. Chronic Cough • Inimmunocompetent patients, 95% caused by – Postnasal drip – Asthma – Gastroesophageal reflux – Chronic bronchitis due to cigarette smoking – Bronchiectasis – Use of angiotensin-converting enzymes inhibitors
- 13.
- 14. Evaluation of ChronicCough • History – Character of cough, quality of the sound and the timing of cough (except the absence during sleep) have not shown to be useful • Physical – Oropharyngeal mucous or cobblestone appearance suggests postnasal-drip syndrome – “silent” postnasal-drip syndrome
- 15. Evaluation of ChronicCough • Heartburn and regurgitation suggest Gastroesophageal reflux disease – “silent”GERD in up to 75% of patients • Irwin,Chest 1993;104:1511-1517 • Wheezing suggests asthma – “silent”asthma (cough variant asthma) in up to 57% of cases • Irwin, Am Rev Respir Dis 1981;123:413-417
- 16. Evaluation of ChronicCough • Where to start – CXR: normal is consistent with PND, GERD, asthma, chronic bronchitis. • Unlikely : bronchogenic carcinoma, sarcoid, TB and bronchiectasis – Since PND syndromes are most common--- start there • Sinusitis or rhinitis of the following varieties: nonallergic, allergic, postinfectious, vasomotor, drug-induced and environmental-irritant induced
- 17. Chronic Cough -PND • PND is by far the most common cause of chronic cough • Since the signs and symptoms are nonspecific, the definitive diagnosis cannot be made by History and Physical examination alone • Therapy – 1st generation antihistamine + a decongestant
- 18. Therapy • Remember –“The newer-generation H1 antagonist do not appear to be effective when cough induced by postnasal drip is not mediated by histamine” • Irwin, Consensus Report of the American College of Chest Physicians. Chest 1998;114:suppl:133S-181S.
- 19. Chronic Cough –Asthma • Cough can be the only symptom of asthma in up to 57% of patients—cough- variant asthma • +/- airflow obstruction on PFT’s • Therapy – If severe, PO steroids followed by inhaled steroids for 6-8 weeks with β2 agonist – If mild, inhaled steroids with β2 agonists
- 20. Chronic Cough --GERD • Etiology – Gross aspiration including pulmonary aspiration syndromes, abscess, chronic bronchitis, bronchiectasis, and pulmonary fibrosis – Laryngeal inflammation – Vagally mediated distal esophageal- tracheobronchial reflex
- 21. Chronic Cough --GERD • When GERD is cause of chronic cough, up to 75% of patients have no GI symptoms • Empiric therapy can if tried if – GI complaints compatible with GERD or – No GI complaints with normal CXR, no ACEI, patients who do not smoke and in whom PND and asthma have been eliminated. • Improvement may take 2-3 months to begin • MEAN TIME TO RECOVERY IS 161-179 DAYS.
- 22. Chronic Cough --ACEI • Class effect of drug; not drug related • Incidence of 0.2 to 33%; – True incidence ≈ 10% • Cough may appear within a few hours up to months after taking the first dose – Pathogenesis seems be an accumulation of inflammatory mediators: bradykinin, substance P and/or prostaglandins. • Therapy – STOP ACEI – Other therapies include oral sulindac, ASA, indomethacin and even oral iron.
- 23. Chronic Cough --ACEI
- 24. Chronic Cough --ACEI
- 25. Cough therapy Principles
- 26. Treatment of cough •Cough is a useful physiological mechanism that serves to clear the respiratory passages of foreign material and excess secretions. – It should not be suppressed indiscriminately. • There are, however, many situations in which cough does not serve any useful purpose – Instead it only annoys the patient or prevents rest and sleep. • Cough may be – i) Un productive (dry) cough OR
- 27. Treatment of cough •It is suggested that irritation of the bronchial mucosa causes bronchoconstriction: • This, stimulates cough receptors. – ( which probably represent a specialized type of stretch receptor) located in the tracheobronchial passages.
- 28. Specific treatment approachto cough • 1) Upper / lower respiratory – Appropriate antibiotics tract infections • 2) Smoking/chronic bronchitis – Cessation of smoking • 3) Pulmonary tuberculosis – Antibiotics • 4) Asthmatic cough – Inhaled β2-agonists/ipratropium/corticosteroid • 5) Postnasal drip (sinusitis) – Antibiotics, nasal decongestants, antihistamines
- 29. Treatment of Cough • Antitussives (cough centre suppressants) • Antihistamines • Bronchodilators • Pharyngeal Demulcents • Expectorants, Mucokinetics & Mucolytics
- 30. Antitussives (cough centre suppressants) • Drugs suppress cough & produces symptomatic relief • MOA – Mainly suppress cough centre in medulla (both central & peripheral effects) • E.g., Opoid drugs (codeine, pholcodeine, noscapine, dextromethorphan) – Opioid = most effective for cough.
- 31. Codeine • Codeine= prodrug⇒ metabolized to morphine – It is an alkaloid found in Opium poppy plant • Has less addiction + resp. centre depressant action – Has useful antitussive action at low doses (<15 mg) • Produce drowsiness, thickening of sputum & • constipation
- 32. Noscapine & Pholcodeine •Related to papaverine • Do not have addictive, analgesic & constipating properties • Do not interfere with mucocilliary movement – Noscapine (15 mg) & – pholcodeine (10 mg)=syrup
- 33. Dextromethorphan • Available insyrup, tablets, spray forms • MOA – NMDA receptor antagonist • Uses – Cough suppressant, temporary relief of cough caused by minor throat & bronchial irritation (accompanies with flu & cold), pain relief • Adverse Effects – Nausea, vomiting, drowsiness, dizziness, blurred vision.
- 34. Antihistamines • Added toantitussives / expectorant formulation – Due to sedative & anticholinergic actions produce relief in cough but lack selectivity for cough centre – No expectorant action =▼secretions (anticholinergic effect) • Suitable for allergic cough (not for asthma) – E.g., Chlorpheniramine, diphenhydramine, promethazine.
- 35. Bronchodilators • Bronchospasm orstimulation of pulmonary receptors = induce or aggravate cough + bronchoconstriction • e.g. β2-agonist (salbutamol, terbutaline) • MOA of bronchodilators in cough – ▲surface velocity of air flow during cough→ Clear secretions of airway – Not used routinely for every type of cough but only when bronchoconstriction is present
- 36. Pharyngeal demulcents • Soothethe throat (directly & also by promoting salivation) – ▼ afferent impulses from inflamed/irritated pharyngeal mucosa • Provide symptomatic relief in dry cough arising from throat – E.g. lozenges, cough drops, glycerine, liquorice, honey
- 37.
- 38.
- 39. Mucoactive agents A closer look
- 40.
- 41. Muco-ciliary Blanket • Innerlining of bronchi – 95% water, 2% glycoproteins – Gel layer-high viscosity from goblet cells – Sol layer – low viscosity from submucosal bronchial glands
- 42. Muco-ciliary Blanket • Bothgoblet cells and bronchial sub- mucosal glands increase secretion when irritated. • Vagal stimulation will also increase bronchial sub- mucosal gland secretion.
- 43. Muco-ciliary Blanket • Increasedgoblet cell secretion = – Increased sputum viscosity. • Increased bronchial sub-mucosal gland secretion = – Decreased sputum viscosity
- 44. Mucus Layer • Gel(1 to 2 µm): Gelatinous and sticky (flypaper) • Sol (4 to 8 µm): Watery, Cilia in this layer – Total layer thickness: 5 to 10 µm thick • Surface Epithelial Cells – Pseudostratified ciliated columnar – Surface goblet cells (6,800/mm 2) – Serous cells – Sol layer – Clara cells – Unknown function (enzymes?) • Submucosal Gland – Bronchial Gland
- 45. Mucus Layer • BronchialGland – Found in submucosa – Found down to terminal bronchioles – Parasympathetic control (Vagus nerve) – Provide the majority of mucus secretion – Total volume 40 times greater than goblet cells
- 46. Function of Mucociliary Escalator • Protective function – Remove trapped or inhaled particles and dead or aging cells. – Antimicrobial (enzymes in sol/gel) – Humidification – Insulation (prevents heat and moisture loss) • NOTE: No cilia or mucus in lower airways (respiratory bronchioles on down) • Mucus also protects the epithelium from toxic materials.
- 47. Structure and Compositionof Mucus • Composition – 95% water • Need for water intake to replenish • Mucus doesn’t easily absorb water once created – 3% protein and carbohydrates – 1% lipids – Less than 0.3% DNA
- 48. Structure and Compositionof Mucus • Glycoprotein – Large (macro)molecules – Strands of polypeptides (protein) that make up the backbone of the molecule • String of amino acids – Carbohydrate side chains – Chemical bonds “hold” mucus together • Intramolecular: Dipeptide links – Connect amino acids • Intermolecular: Disulfide and Hydrogen bonds – Connect adjacent macromolecules
- 50. Mucus Production • Normalperson produces 100 mL of mucus per 24 hour period – Most is reabsorbed back in the bronchial mucosa – 10 mL reaches the glottis – Most of this is swallowed • Mucus production increases with lung disease
- 51. Increased Mucus Production • Smoking • Environmental irritants • Allergy • Infections • Genetic predisposition • Foreign bodies
- 52. Increased Mucus Production ↑ Viscosity of mucus ↓ Ciliary effectiveness ↑ Mucus plugs ↑ Airway Resistance ↑ Infections Obstructed bronchioles leads to atelectasis
- 53. Diseases that IncreaseMucus Production • Chronic Bronchitis • Asthma • Cystic Fibrosis • Acute Bronchitis • Pneumonia • Also some drugs (anticholinergics, antimuscarinics)
- 54. Factors that ImpairCiliary Activity • Endotracheal tubes • Temperature extremes • High FiO2 levels • Dust, Fumes, Smoke • Dehydration • Thick Mucus • Infections
- 55. Viscosity and Elasticity •Rheology • Viscosity: Property of a liquid that measures the resistance to movement when a force is applied. – Increased viscosity, increased resistance to flow • Olive oil vs. Water • Elasticity: Property of solid whereby a solid changes shape (deforms) when a force is applied. – Ideally, a solid is totally elastic, and returns to its original shape when force is released. • The mucus layer is ideally very elastic and has a very low viscosity.
- 56. Mucoactive Agents • Expectorants Hypertonic saline, Guaifenesin • Mucoregulators Carbocysteine, Anticholinergics, Glucocorticoids, Macrolid es • Mucolytics N-Acetylcysteine, N-Acysteline, Erdosteine, Dornase-α, Gelsolin, Tymosin-ß4, Dextran, Heparin • Mucokinetics Broncodilators, Ambroxol, Surfactant
- 57. Hypoviscosity/Wetting Agents: Saline solutions • Normal Saline (.9%) – Isotonic and good diluent for drugs • Half-normal Saline (.45%) – Hypotonic, good diluent, and can be administered via USN • Aerosol solutions tend to increase in tonicity as they go deeper into the lung because of evaporation!
- 58. Hypoviscosity/Wetting Agents: Saline solutions (cont.) • Hypertonic Saline (usually 10%) – Wetting agent – Bronchorrhea (draws fluid from mucosa to dilute gel) – May also help break up mucoprotein-DNA bonds in mucus (mucolytic effect!) • Limitations: – Bronchospasm – Hypernatremia
- 59. Hypoviscosity/Wetting Agents: Sodium Bicarb • Usually 2 – 7.5% solution • Wetting agent and bronchorrhea • Also alkaline pH breaks up hydrogen bonds • Also breaks up calcium bonds • Like hypertonic saline, it is both a wetting agent and a mucolytic • Can usually NOT be used as a diluent for drugs • Has same side effects as hypertonic saline
- 60. Mucociliary Escalator • MucosalBlanket – Sol layer – Gel layer • Cilia – 200 per cell – 6 µm in length – Beat 1000/min – Move mucus 2 cm/min – Paralyzed by cigarette smoke
- 61. Mucus vs. Sputum •Mucus is the total secretion from mucous membranes including the surface goblet cell and the bronchial glands. • Sputum is the expectorated secretions that contains mucus, as well as oropharyngeal and nasopharyngeal secretions (saliva).
- 62. Facilitation of MucusClearance • Provide adequate hydration – Increase fluid intake orally or IV • Remove causative factors – Smoking, pollution, allergens • Optimize tracheobronchial clearance • Use Mucolytics • Reduce Inflammation
- 63. Function of Mucolytics •Weakening of intermolecular forces binding adjacent glycoprotein chains – Disruption of Disulfide Bonds • Alteration of pH to weaken sugar side chains of glycoproteins • Destruction of protein (Proteolysis) contained in the glycoprotein core of proteolytic enzymes – Breaking down of DNA in mucus
- 64. Function of Mucolytics •Disruption of Disulfide Bonds – acetylcysteine breaks the bonds by substituting a sulfhydril radical –HS
- 65. Function of Mucolytics •Alteration of pH – 2% NaHCO3 solutions are used to increase the pH of mucus by weakening carbohydrate side chains – Can be injected directly into the trachea or aerosolized (2-5 mL)
- 66. Function of Mucolytics •Proteolysis – Dornase alfa (Pulmozyme) – Attacks the protein component of the mucus
- 67. Hazard of Mucolytics •The problem with all three mucolytics is that they destroy the elasticity of mucus while reducing the viscosity. • Elasticity is crucial for mucociliary transport. • The patient must be able to cough adequately to remove the mucus.
- 68. Mucolysis • Mucolysis isthe breakdown of mucus. • Mucolysis is needed in diseases in which there is increased mucus production: – Cystic Fibrosis – COPD – Bronchiectasis – Respiratory Infections • Turberculosis
- 69. Mucolysis • These diseasesresult in a marked slowing of mucus transport – Changes in properties of the mucus – Decreased ciliary activity – Both
- 70. Mucolytics • acetylcysteine • sodiumbicarbonate (NaHCO3) • dornase alfa – Pulmozyme
- 71. Mucolytics • Aid mucokinesisby breaking up bonds in mucus & liquefying the viscous tracheobronchial secretions
- 72. Mucolytics • Decrease mucusviscosity, depolymerize DNA / F-actin network – N-Acetylcysteine – breaks disulphide bonds linking mucin polymers. Also antioxidant, anti- inflammatory – Erdosteine – regulates mucus production. Increases mucociliary transport.
- 73. Dairy Intake • Noevidence to support the common belief that drinking milk increases the production of mucus or phlegm and congestion in the respiratory tract • There is a loose cough associated with milk intake
- 74. Secretion Management • Increasethe depth of the sol layer – Water – Saline – Expectorants • Alter the consistency of the gel layer – Mucolytics • Improve ciliary activity – Sympathomimetic bronchodilators – Corticosteroids
- 75. Bland Aerosols • “Dilutes”mucus molecule • Also known as wetting agents – Function may be more of an irritant than a wetter • Types – Sterile & Distilled Water • Humectant • Dense aerosols and asthmatics – Normal (isotonic) Saline – Hypertonic Saline • Increase mucus production – Hypotonic Saline
- 76. Cough Suppressants • Vagalstimulation causes a cough. • Irritation of pharynx, larynx, and bronchi lead to a reflex cough impulse. • If the cough is dry and non-productive, it may be desirable to suppress its activity. • Cough suppressants depress the cough center in medulla (?). – Narcotic preparations (codeine) – Non-Narcotic preparations (dextromethorphan) • Caution in patients with thick secretions.
- 77. acetylcysteine • Indications – Mucolytic by aerosol or direct instillation into the ET tube. – Given orally to reduce liver injury with acetaminophen (Tylenol) overdose. • Mix with cola or given by NG tube.
- 78. Dosage of acetylcysteine •Concentration – 10% or 20% • Dosage – 3-5 mL of a 20% solution TID or QID • Maximum dose 10 mL – 6-10 mL of a 10% solution TID or QID • Maximum dose 20 mL • 1-2 mL of a 10% or 20% for direct instillation
- 79. Hazards of acetylcysteine •Bronchospasm – Asthma – may be a problem during an acute asthma attack. • Anecdotal; lack of evidence – If used with asthma, use 10% and mix with a bronchodilator (preferably a short-acting agent). • Increase mucus production – Be prepared to suction a patient who cannot cough or who is intubated.
- 80. Hazards of acetylcysteine •Do not mix with antibiotics in the same nebulizer (incompatible). • Nausea & Vomiting – Disagreeable odor (smells like rotten eggs) due to the hydrogen sulfide. • Open vials should be used within 96 hours to prevent contamination.
- 81. Expectorants (Bronchomucotropics) •Drugs that increase and aid clearance of respiratory tract secretions • Act peripherally to increase expulsion of mucus from the respiratory tract. – Increase bronchial secretion OR – Decrease its viscosity & facilitate its removal by coughing – Loosen cough ► less tiring & more productive – Hypoviscosity agents (Wetting agents) • Aerosol hypertonic saline – increases secretion volume and/or hydration, may decrease viscosity by diluting the gel layer – Mucolytics
- 82. Classification of Expectorants •Classified into • 2 types: 1. Stimulant expectorants – increase overall mucus volume to enhance clearance. • Directly acting • Reflexly acting 1. Mucolytic expectorants - break down mucus
- 83. Expectorants • Iodides – Unclear function – SSKI (Saturated Solution of Potassium Iodide) • Guifenesin – At high doses, stimulates bronchial gland secretion – Robitussin
- 84. Expectorants (Bronchomucotropics) •Drugs that increase and aid clearance of respiratory tract secretions • Act to stimulate the cholinergic system and ↑ mucus secretion. – Eg. Guaiphenesin - Expectorant drug usually taken by mouth – Available as single & also in combination – MOA=Increase the volume & reduce the viscosity of secretion in trachea & bronchi • Act directly – Ammonium chloride - Gastric irritants = reflexly↑ bronchial secretions + sweating – Sodium citrate &
- 85. Expectorants (Bronchomucotropics) •Drugs that increase and aid clearance of respiratory tract secretions – Usually stimulate sol layer production by direct irritation or indirect through vagal stimulation • Increased sol means decreased viscosity! – Smoke is a bronchomucotropic! Unfortunately, it’s irritation stimulates the bronchial submcosal glands AND the goblet cells so mucus production increases as well as viscosity – Spicy food causes increased sol due to vagal stimulation!
- 86. N-Acetylcysteine • Given directlyinto respiratory tract as 10 or 20% solution (hypertonic and alkaline pH) • MOA of acetylcysteine – Opens disulfide bond in mucoproteins of sputum =↓ viscosity (most effective form of mucolysis) – Also breaks mucoprotein bonds and hydrogen bonds • Bronchorrhea
- 87. N-Acetylcysteine • Onset ofaction quick---used 2-8 hourly • Uses – Cystic fibrosis (to ↓viscosity of sputum) • Adverse effects – Nausea, vomiting, bronchospasm in bronchial asthma.
- 88. Pulmozyme (Dornase Alphaor DNAse) • Excellent aerosol mucolytic for cystic fibrosis patients • Lyses the DNA bonds in the sputum of cystic fibrosis patients – These patients have a lot of such bonds!
- 89. Mucolytic treatment inacute exacerbations : • Mucolytic drugs have a small effect in decreasing acute exacerbations. • Improvement of subjective complaints – Decrease of inflammatory markers – Bacterial eradication – They are not effective on FEV1 decline. – They may have some effects on frequent exacerbators requiring hospitalization BUT no difference on hospitalization length.
- 90. Mucoregulators • Agents regulatingmucus secretion or interfere with the DNA/F-actin network – Carbocysteine - regulates mucus visco-elasticity. Also antioxidant, anti-inflammatory – Anticholinergics- inhibits cholinergic system which ↑ mucus secretion (M3 res). – Glucocorticoids – decrease airway inflammation and mucus secretion. – Macrolides – ↓ airway inflammation & mucus secretion.
- 91. Mucokinetics • Agents usedwhen secretions ↑ in amount and/or viscosity to ↑ the mucociliary transport – Bronchodilators - Improves cough by increasing expiratory flow and increase in secretion expulsion, Also antioxidant, antiinflammatory – Bromhexine – Ambroxol-increases in surfactant production, inhibits chloride channels, Decrease in viscosity of secretions – Surfactant –decreases surface adhesion between mucus and airway.
- 92. Bromhexine • MOA ofBromhexine – Synthetic derivative of vasicine (alkaloid= Adhatoda vasica) – Thinning & fragmentation of mucopolysaccaride fibers – ↑ volume & ↓ viscosity of sputum
- 93. Ambroxol • Ambroxol Hydrochlorideis the active metabolite of Bromhexine & works as – Secretolytic agent used in the treatment of viscid or excessive mucus. – Mucoactive drug with several properties including secretolytic and secretomotoric actions that restore the physiological clearance mechanisms of the respiratory tract, – Stimulates synthesis and release of surfactant by type II pneumocytes. Surfactant acts as an anti- glue factor by reducing the adhesion of mucus to the bronchial wall, in improving its transport.
- 94. Ambroxol • Ambroxol allowspatients to breathe freely and deeply by: – Promoting mucus clearance, – Facilitating expectoration and – Easing productive cough. • Anti-inflammatory properties of Ambroxol lead to ↓ of redness of the sore throat and thus, ambroxol relieves pain in acute sore throat, with a fast onset of action and a long duration of effect of at least 3 hours.