Bronchitis%20-%20chronic%20in%20acute%20exacerbation Treatment

• Rapid resolution of symptoms
  • Reduce mucus overproduction and inflammation
  • Decrease mucus viscosity and increase ciliary transport
  • Facilitate cough mechanism
• Prevent transient loss of pulmonary function
• Reduce the bacterial burden in the lower respiratory tract
• Prevent relapse or lengthen the time between exacerbations
• Re-evaluation of the disease to reduce the risk of future exacerbations

Bronchodilators

• Bronchodilators should be used for the treatment of dyspnea accompanying an exacerbation

Short-Acting Anticholinergics (Inhaled)

• Eg Ipratropium bromide
• Effects: An effective bronchodilator with a slower onset of action and a slightly longer duration of action compared to short-acting beta₂-agonists, but no appreciable difference between the two in terms of effects on pulmonary function
  • Decreased cough frequency and sputum volume have been noted in patients using Ipratropium
  • Side effects may be fewer compared to Salbutamol
• Available in metered-dose inhalers (MDIs) and nebulizer solution
  • There is no significant difference in pulmonary function outcomes between delivery system, but in most situations, MDIs with an appropriate spacer would be preferred

Short-Acting Beta₂-Agonists (Inhaled)

• Short-acting inhaled beta₂-agonists are usually the preferred bronchodilators
  • Addition of anticholinergics is recommended should there be no prompt response with inhaled beta_2-agonists
• Produce effective bronchodilatation with a faster onset of action than anticholinergics, but no appreciable difference between the two in terms of effects on pulmonary function
• Available in MDI and nebulizer solution
• The role of long-acting beta₂-agonists has not been studied in AECB therefore are not recommended for treatment of the condition at the present time

Methylxanthines

• The use of methylxanthines in AECB is not indicated
  • The addition of Aminophylline to inhaled bronchodilators does not appear to improve FEV₁
•  Patients already on methylxanthines should continue the medications but monitor for drug interactions with antibiotics

Corticosteroids

• The use of oral or parenteral steroids is supported for most patients with moderate to severe AECB
• Action: Reduce airway edema and mucus hypersecretion
• Effects: Rapid improvement in pre- and post-bronchodilator FEV₁, rapid recovery of partial pressure of O₂, decreased treatment failures, shorter hospitalization rates, speed up recovery in AECB and may reduce the frequency of exacerbations and likelihood of relapse

Inhaled Corticosteroids

• Recommended in stable patients when airflow obstruction is severe or very severe (eg FEV₁ <50%) and when there is a history of frequent exacerbations

Systemic Corticosteroids

• Beneficial in cases of significant pulmonary compromise, particularly if the patient requires hospitalization
• Treatment is recommended for 5-14 days
• The exact dose and duration of therapy should be individualized
  • Eg The use of high-dose and prolonged steroids must be carefully weighed in the elderly patients
  • Prednisone PO is usually used initially at a dosage of 0.5-1.0 mg/kg/day and then tapered at a rate and duration based on response
• IV corticosteroids may be used initially in severely ill patients or in patients who are unable to take oral medications
• In studies, the major side effect in the steroid-treated group was hyperglycemia

Empiric Antibiotic Therapy

Based on the current available evidence, antibiotic therapy should be given in patients with exacerbations of chronic obstructive pulmonary disease (COPD) if:

• With presence of at least two out of three cardinal symptoms (increased dyspnea, increased sputum purulence and increased sputum volume)
• Two of the cardinal symptoms are present with increased sputum purulence as one of the two symptoms
• The exacerbation is severe requiring mechanical ventilation (invasive or non-invasive)
• The recommended duration of therapy is 5-7 days
  • Short-duration antimicrobial treatment is as effective and safer than long-duration therapy and is associated with fewer adverse events, better compliance, reduce risk of development of bacterial resistance and lower costs

Therapy should be based on local resistance patterns along with patient risk stratification to prevent therapeutic failure

• Some studies have shown that severity of bronchitis is an important determinant of the type of pathogen
  • S pneumoniae predominates in patients with mild exacerbation
  • H influenzae and M catarrhalis are the frequent pathogens as FEV₁ declines and patients have more frequent exacerbations and/or comorbid diseases
  • P aeruginosa may be present in those with severe airway restriction
• Antibiotics used should have significant in vitro and in vivo activity against the pathogens most commonly associated with AECB, including H influenzae, S pneumoniae and M catarrhalis, with minimal adverse effects and good penetration into sputum and bronchial mucosa
•  In patients with more severe airway obstruction, coverage may need to be extended to include other potential pathogens (eg Gram-negative bacilli)
• Aminopenicillins, Co-trimoxazole and Doxycycline are considered first-line antibiotics for AECB
  • Emergence of antimicrobial resistance in bacteria frequently associated with acute exacerbations of chronic bronchitis have limited its use
• Amoxicillin/clavulanic acid, macrolides, second or third generation cephalosporins and quinolones are good alternatives in areas with increasing antibiotic resistance to older agents
  • Associated with fewer clinical failures compared with use of first-line agents

Aminopenicillins

• Recommendation for treatment of simple AECB with aminopenicillins is justified since there are no clinical or pharmacoeconomic studies showing the advantage of more potent agents
• No activity against atypical and beta-lactamase-producing pathogens, limited activity against Enterobacteriaceae
• High dose is effective against Penicillin-resistant S pneumoniae

Aminopenicillin/Beta-lactamase Inhibitors

• Covers major bacterial pathogens including beta-lactamase-producing pathogens, moderate activity against Enterobacteriaceae, but no activity against atypical pathogens
• High dose of Aminopenicillin component is effective against Penicillin-resistant S pneumoniae
• Short-term effectiveness of Amoxicillin/clavulanic acid is equivalent to that of macrolides and quinolones

Cephalosporins (Second and Third Generation)

• If resistant S pneumonia and H influenzae is a concern, selected 2nd and 3rd generation cephalosporins may be preferred over older agents
• Offer enhanced stability against beta-lactamases of H influenzae, H parainfluenzae and M catarrhalis and improved efficacy against Penicillin-susceptible S pneumoniae and Methicillin-susceptible S aureus

Co-trimoxazole (Sulfamethoxazole [SMZ] and Trimethoprim [TM])

• Recommendation for treatment of simple AECB with Co-trimoxazole is justified since there are no clinical or pharmacoeconomic studies showing the advantage of more potent agents
• Covers major bacterial pathogens, no activity against atypical pathogens and resistance in S pneumoniae is common; resistance limits its usefulness
• May be an acceptable alternative for patients who are allergic to Penicillin

• Recommendation for treatment of simple AECB with Doxycycline is justified since there are no clinical or pharmacoeconomic studies showing the advantage of more potent agents
• Covers major bacterial and atypical pathogens, but S pneumoniae resistance is common
• Alternative to quinolones and macrolides when atypical coverage is required
• Acceptable as an alternative for patients who are allergic to Penicillin, cephalosporins and newer macrolides

Advanced Macrolides

• If resistant S pneumoniae and H influenzae are a concern, advanced macrolides may be preferred over older agents
• Active against atypical pathogens, not active against Enterobacteriaceae, and macrolide-resistant S pneumoniae is common but this does not appear to reduce clinical effectiveness
• Reasonable option in beta-lactam allergic patients

Quinolones

• Has good tracheobronchial penetration
• Cover all major bacterial and atypical pathogens as well as Enterobacteriaceae and some agents cover P aeruginosa
• Quinolones with enhanced activity to drug-resistant S pneumoniae are preferred
  • Eg Levofloxacin, Moxifloxacin
• Ciprofloxacin
  • Considered first-line agents in ambulatory AECB patients only if P aeruginosa coverage is required
  •  Least active against S pneumoniae and should not be used routinely in the management of AECB; most active against P aeruginosa

Other Pharmacotherapy Agents

• Expectorants/cough suppressants have not been shown to improve lung function or hasten the clinical recovery but may produce a subjective improvement
• Chronic use of mucolytics helps reduce the frequency of exacerbations and days of illness but does not improve ventilatory function
• Chest physiotherapy has not been shown to improve lung function or hasten clinical recovery in AECB
• There is still no evidence supporting the use of leukotriene receptor antagonists in AECB
• Nitrogen cryospray and rheoplasty can potentially treat chronic bronchitis by stimulating regeneration of normal epithelium in the central airways