Untitled

Bajraktar
evic, Jakob
Respiratory
pocket
2nd Edition
RESPIRATORY DISEASES
Obstructive Lung Diseases
Definition
* Asthma is a chronic inflammatory disease of the airways resulting in airflow obstruction secondary to airway edema, increased mucus production, bronchospasm and infiltration of the airway with leukocytes (eosinophils, lymphocytes and neutrophils). It is usually reversible either spontaneously or with treatment * Status asthmaticus: severe acute asthma attack refractory to optimal treatment
Statistics
* Prevalence: affects ~ 5% of US population (up to 10% of children) and m 10%
* Mortality: 5000 - 6000 deaths/year
Etiology
* Allergic: begins early in life; results from exposure to antigens such as pollen,
certain foods, smoke, pollutants e IgE activation e antigen- antibody reaction involving pulmonary inflammatory response; genetic * Nonallergic: usually of later onset (> 35 years); secondary to respiratory infections,
anxiety, irritant gases, pollutants, exercise in cold weather, large changes in Pb and temperature, strong emotion (laughing, crying, etc) and drugs (aspirin, β-blockers) Pathology
* Many cells (mastcells, lymphocytes, macrophages, etc.) and their mediators (histamine, leukotrienes, etc) play a role in causing bronchoconstriction and edema, resulting in o airway diameter and m Raw * Pathological changes: (1) Hypertrophy of airway smooth muscle (2) Hyperplasia of mucus glands and goblet cells e hypersecretion (3) Inflammation (edema) (4) Subepithelial collagen deposition (airway remodeling) in some patients = airflow obstruction; may be partially reversible www. media4u .com
8. Obst ructive L ung Dise ases
Clinical manifestations
Signs and symptoms:
* Dyspnea
* Wheezing (all that wheezes is NOT asthma; wheezing may also occur with COPD,
CHF, aspiration, upper airway obstruction and vocal cord dysfunction) * Cough
* Chest tightness
* Retractions in children * ± Cyanosis, diaphoresis * m Expiratory time
* Pulsus paradoxus: o sysBP by > 10 mmHg on inspiration
ABG:
o PaO2, o PaCO2 (m in severe attack)
PFT:
* o Expiratory flows: o FVC, FEV1, FEV1/FVC
* m Lung volumes: m RV, TLC, FRC, secondary to air trapping
* Normal DLCO
Diagnosis
* Bronchoprovocation test: test for airway hyperreactivity. Patient inhales
progressively higher doses of bronchoconstricting agent such as histamine or methacholine. After each dose, FEV1 is measured and dose that causes o FEV1 by 20% is known as provocative dose (PD 20). d p. 64 * Pre- and post-bronchodilator: m FEV1 by > 12 - 15% and > 200 ml
* DLCO: normal in asthma (and chronic bronchitis); o in emphysema
Monitoring
* Peak expiratory flow rate (PEFR):
) Difference of > 20% between morning and afternoon PEFR may suggest asthma ) Severe bronchospasm: PEFR < 100 L/min
) Extreme danger: PEFR < 60 L/min
* Sputum eosinophilia: marker of airway inflammation; asthmatic patients with
higher sputum eosinophilia are likely to benfit from corticosteroid therapy * Exhaled nitric oxide: higher exhaled nitric oxide levels predict airway
Differential diagnosis
* COPD: may coexist with asthma or it may have a reversible component
* Pulmonary edema (cardiac asthma)
* Large airway obstruction: foreign body, tumor, tracheal stenosis, vocal cord
* May also consider: cystic fibrosis, bronchiolitis, pneumonias (aspiration), * In children, it is distinguished from bronchiolitis because it responds to Treatment
1. Prevent:
Attacks by avoiding triggers
2. Oxygen:
For hypoxemia
3. Quick relief medications:
) Short-acting β2 agonists (albuterol, levalbuterol, metaproterenol) are 1st line ) Anticholinergics (Atrovent) are 2nd line defense which may be added to
β2 agonist, possibly enhancing actions of the latter ) Systemic corticosteroids (prednisone, prednisolone, methylprednisolone) for
acute exacerbations nonresponsive to bronchodilators ) ± Theophylline
4. Long-term control medications:
) Inhaled corticosteroids (beclovent, budesonide, fluticasone) to prevent
long-term symptoms. Spacer should be used and mouth rinsed after dose to o risk of oral candidiadis ) Long-term β2 agonist (salmeterol [Serevent]) may be useful in nocturnal asthma
) Theophylline as an adjunct to anti-inflammatory drugs
) Cromolyn sodium may be useful for allergy and exercise-induced asthma
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8. Obst ructive L ung Dise ases
) Anti-leukotrienes may be of use in mild asthma:
- Accolate (Zafirlukast) - Singulair (Montelukast) - Zyflo (Zileuton) ) Xolair (Omalizumab):
Binds to circulating IgE antibodies e o amount of IgE antibodies available to bind to mast cells. Therefore, it blocks allergic reactions - Indication: patients > 12 years old with moderate-to-severe persistent (allergic) asthma who get very little or no relief from standard asthma medications 5. Heliox:
A mixture of helium and oxygen (80% helium: 20% oxygen or 70% helium:
30% oxygen) is a controversial alternative therapy for severe acute asthma attack.
It is usually administered in the emergency department. See chapter on medical gases
for further information on He-O2 gas therapy.
6. Intubation/MV:
) For respiratory failure (RF) and status asthmaticus ) Only about 5% of all hospitalized asthma patients require intubation and mechanical ventilation and most intubated patients usually recover rapidly with treatment; most of these patients can be extubated within 2 - 3 days ) Predictors:
- Severe hypoxemia on FIO2 > 0.5, PaCO2 > PaO2, pH < 7.25 - o/absent breath sounds- PEFR < 50%- Nasal flaring and RR > 40/min in children ) Goals of mechanical ventilation:
Provide acceptable gas exchange and avoid air trapping. This pulmonary hyperinflation can lead to hypotension. Generally, VT of 5 - 8 ml/kg (maintain Pplat < 30 cmH2O) and inspiratory flow > 80 L/min help reduce the risk of alveolar overdistension and air trapping 7. Stepwise approach for managing asthma in adults and children
> 5 years old
Classify severity: clinical feature before Symptoms/day PEF or FEV1 Daily medications (dark gray shaded
Symptoms/night PEF
variability
persistent
AND, if needed,* Corticosteroid tablets or syrup long term (2 mg/kg/d, not > 60 mg/d). [Make repeat attempts to o systemic corticosteroids and maintain control with high-dose inhaled corticosteroids] moderate
persistent
corticosteroids AND either leukotriene modifier or theophylline www. media4u .com
8. Obst ructive L ung Dise ases
moderate
persistent
medium-dose range AND add long-acting inhaled β2 agonist OR medium-dose range AND add either leukotriene modifier or theophylline persistent
nedocromil or sustained release theophylline to serum concentration of 5 - 15 µg/ml intermit-
normal lung function and no symptoms. A course of systemic corticosteroids is recommended Quick relief: all patients:
* Short-acting inhaled β2 agonist bronchodilator:
* Intensity of treatment will depend on severity of exacerbation: up to 3 treatments at 20 min intervals or a single nebulizer treatment as needed. Course of systemic corticosteroids may also be needed * Use of short-acting β2 agonists > 2 x/week in intermittent asthma may indicate the need to initiate (increase) long-term therapy * Step down: Review treatment every 1 - 6 months; a gradual stepwise reduction
* Step up: If control is not maintained, consider step up. First, review patient
medications technique, adherence and environmental control * The stepwise approach is meant to assist, not replace, the clinical decision- making required to meet individual patient needs * Refer to asthma specialist if there are difficulties controlling asthma or if Source: NIH Expert Report Panel 2, Guidelines Publications (Selected Update of 1997 Guidelines) No. 97-4051 2002. 8. Stepwise approach for managing infants and young children
< 5 years old with acute or chronic asthma
Classify severity: clinical features before Medications required to maintain long-treatment or adequate control Symptoms/day
Daily medications (dark gray shaded
Symptoms/night
persistent
AND, if needed,* Corticosteroid tablets or syrup long term (2 mg/kg/d, not > 60 mg/d).
[Make repeat attempts to o systemic corticosteroids and maintain control with high-dose inhaled corticosteroids] moderate
persistent
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8. Obst ructive L ung Dise ases
moderate
persistent
If needed: recurring severe exacerbations and either leukotriene receptor antagonist or theophylline persistent
with holding chamber with or without face mask or dry powder inhalers [DPI]) with holding chamber) OR leukotriene receptor anatagonist intermittent
Quick relief: all patients
* Bronchodilator as needed for symptoms; preferred: short-acting inhaled
β2 agonist by nebulizer or face mask and space/holding chamber; alternative:
oral β2 agonist
* With viral respiratory infection: bronchodilator q4 - 6 h up to 24 h (longer with physician consult); generally, repeat no more than once every 6 weeks. Consider systemic corticosteroid if exacerbation is severe or patient has history of previous severe exacerbations * Use of short-acting β2 agonists > 2 x/week in intermitt. asthma (or m use in persistent asthma) may indicate need to initiate (increase) long-term controlling therapy NOTE: Same as for stepwise approach in adults and children > 5 years old; also,
there are very few studies on asthma therapy for infants.
Source: NIH Expert Panel Report 2, Guidelines Publications (Selected Update of 1997 Guidelines) 9. Usual dosages for long-term control medications
Medication
Dosage form
Adult dose
Child dose*
Inhaled corticosteroids
(See estimated daily dosages for inhaled corticosteroids below)
Systemic corticosteroids (applies to all 3 corticosteroids)
prednisolone
Prednisolone
5 mg tab * Daily in single dose or qod. as needed 5 mg/5 ml Prednisone
Long-acting inhaled β2 agonists (Should not be used for symptom relief or
exacerbations. Use with inhaled corticosteroids)
Salmeterol
Formoterol
Combined medications
Fluticasone/
Salmeterol
Cromolyn and Nedocromil
Cromolyn
Nedocromil
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8. Obst ructive L ung Dise ases
Leukotriene Modifiers
Montelukast
5 mg qhs (6 - 14 years)10 mg qhs (> 14 years) Zafirlukast
Zileuton
Methylxanthines
(target serum concentration of 5 - 15 µg/ml at steady state)
Theophylline
10. Estimated comparative daily dosages for inhaled corticosteroids
Low daily dose
Medium daily dose High daily dose
Adult/Child*
Adult/Child*
Adult/Child*
Beclomethasone CFC 168 - 504 µg
Beclomethasone HFA 80 - 240 µg
Budesonide DPI
Flunisolide
Fluticasone
Triamcinolone
acetonide
11. Managing asthma exacerbations: emergency department and
hospital-based care (NIH 1997)
History, physical examination (breath sounds [BS], accessory muscle use, HR, RR), O2sat, PEF or FEV1 Repeat examination, PEF, O2sat, other tests as needed www. media4u .com
8. Obst ructive L ung Dise ases
Chronic Obstructive Pulmonary Disease (COPD)
Progressive airflow obstruction (o expiratory flow) which may be partially reversible, unlike the reversible airway obstruction found in asthma.
Includes chronic bronchitis or emphysema or both and sometimes asthma that has an irreversible component. Chronic bronchitis
* Defined clinically as a chronic productive cough on most days for m 3 months for
* It causes airflow limitation by narrowing the airways with mucosal thickening and excessive amounts of mucus due to hyperplasia of mucus producing glands Emphysema
* Defined histologically as the permanent dilation of air spaces distal to terminal
bronchioles by destruction of alveolar walls/lung parenchyma e o elasticity * It causes airway obstruction by o elasticity (elastic recoil) = airways close prematurely on expiration. Normally, elastic recoil holds the airways inflated on expiration * Patients who have pure emphysema uncomplicated by chronic bronchitis have 222 19. Respiratory Drugs
THERAPEUTICS
Respiratory Drugs
Bronchodilators (BDs)
Adrenergic agents (Sympathomimetics)
MA: stimulate β2- receptors e activation of 3',5' cAMP e relaxation of airway
smooth muscle
AE: tremors, palpitations, mild hypertension, tachycardia, tolerance if excessive,
excessive use e o K+ e arrhythmias
Albuterol
DPI: 200 µg cap; q4 - 6 hTab: 2 mg, 4 mg, tid, qid (extended release tab 4 mg, 8 mg, q12 h) Ped: 1.25 - 2.5 mg/dose via nebInfant: 0.1 mg/kg/doseNB: 0.1 - 0.5 mg/kg/dose q2 - 6 h Bitolterol
Prodrug hydrolyzed
in lungs into colterol
Bronchodilators (BDs) 223
Epinephrine
Formoterol
bronchospasm. Long-acting BD for maintenance therapy (similar to salmeterol but very quick onset) Isoetharine
Neb: 0.25 - 0.50 ml in onset: < 5 min Inactivated by heat,
light, air - turns pink:
discard (sputum may
tinge pink)
Isoproterenol
short duration and availability of better BDs Levalbuterol
Neb: > 12 years: 0.63 Strong β2 onset: Less β1 than albuterol = o AE + m duration Metaproterenol Neb: 0.2 - 0.3 ml in
Pirbuterol
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224 19. Respiratory Drugs
epinephrine
vasoconstrictor for
Salmeterol
bronchospasm. Long-acting BD for maintenance therapy of asthma Terbutaline
tocolysis - inhibition
Anticholinergic agents (Parasympatholytics):
MA: inhibit smooth muscle contraction by blocking muscarinic receptors to
o cGMP and Ach release. Also, o mucus secretion.
AE: dry mouth, blurred vision, cough
Caution: in patients with glaucoma, prostatic hypertrophy or bladder obstruction
Ipratropium
± asthma. Also comes
premixed with
albuterol for neb
(DuoNeb) and MDI
(Combivent)
Corticosteroids (CS) 225
Atropine
NOT used any more
such as: m mucus thickness, blurred vision, m HR, hallucinations, etc.
Tiotropium
NOT approved yet in
Methylxanthines:
MA: not clear; inhibit phosphodiesterase e m cAMP e bronchial smooth muscle
relaxation. There are other theories
EF: m diaphragm contraction, m mucociliary action, m resp center drive, m CO,
+ve inotropic and chronotropic effect, m myocardial muscle perfusion, o PVR,
m diuresis
AE: has narrow therapeutic dose (5 - 15 µg/ml); toxicity with > 20 µg/ml: seizure,
nausea, arrhythmia, diarrhea, convulsions, irritability, hyperglycemia
Aminophylline
patients due to its dilating effects (see mod-severe asthma; infant apnea (also caffeine) Corticosteroids (CS)
Corticosteroids are potent anti-inflammatory drugs. They are mainly used for asthma and acute exacerbation of COPD. Other uses include: sarcoidosis and other ILDs, chemical pneumonitis, cancer (CA), rheumatoid arthritis and for mothers delivering premature infants, in order to stimulate the baby's surfactant production and o IRDS risk.
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226 19. Respiratory Drugs
Inhaled corticosteroids:
MA: help alleviate airway obstruction by: o inflammation,m β2 agonist
responsiveness and o/prevent hypersensitivity reactions
EF: 6 - 12 h into therapy (NOT for acute asthma attack)
AE: using inhaled steroids e o AE of systemic steroids (see systemic corticosteroids,
below); inhaled CS may cause cough, hoarseness and fungal infection (Candida) in
the oropharynx. Ensure that patient rinses mouth after therapy and add spacer to
MDI to o risk
Beclomethasone
MDI: 2 puffs tid, qid of 42 µg (max 20 puffs/d); Budesonide [Pulmicort
DPI: 1 - 4 inh bid of 200 µgNeb: 0.25 - 0.50 mg/2 ml Dexamethasone
MDI: 3 puffs of 84 µg tid, qid (1st MDI steroid in USA; NOT used often since advent of newer steroid agents) Flunisolide [Aerobid]
Fluticasone [Flovent,
MDI: 2 - 4 puffs bid of 44, 110 or 220 µg/puff DPI: 1 - 2 inh bid of 50, 100 or 250 µg/inh (also comes combined with Serevent in DPI called Advair) Triamcinolone
MDI: 2 puffs tid, qid or 4 puffs bid (of 100 µg/puff), max 16 puffs/d; (comes with built-in spacer) Systemic corticosteroids:
AE: long-term use: immunosuppression, osteoporosis, fluid retention, hypo-
thalamo-pituitary-adrenal suppression, skin bruising, cataract, myopathy of skeletal
muscle, glaucoma, Cushing's syndrome (obesity, moon face, buffalo hump in upper
back), growth inhibition in children?; short-term use: mood changes (euphoria,
delirium), hyperglycemia, stomach upset, insomnia, agitation,m appetite
Betamethasone
Ind: to hasten fetal lung maturity, inflammatory Cortisone [Cortone]
Ind: adrenal insufficiency, inflammatory disease Dexamethasone
Ind: to hasten fetal lung maturity, cerebral edema, Hydrocortisone [Cortef,
Ind: adrenal insufficiency, inflammatory disease Asthma/COPD Combinations 227
Methylprednisolone
Ind: acute severe asthma, anaphylaxis, lupus nephritis, spinal cord injury; [PO, IM, IV] Prednisolone [Prelone]
Ind: acute severe asthma; dose: 5 - 60 mg PO/IV/IM qid; (in children: 1 - 2 mg/kg/d) Prednisone [Deltasone]
Ind: asthma exacerbations; dose: 5 - 60 mg PO qid (tab: 1, 5, 10, 20, 50 mg or sol 5 mg/5 ml) Triamcinolone
Ind: inflammatory disease, dose: 4 - 48 mg/d PO/IM Asthma/COPD Combinations
Fluticasone + salmeterol
Albuterol + ipratropium [Combivent]
Albuterol + ipratropium [DuoNeb]
Neb: 3 mg albuterol + 0.5 mg ipratropium premixed/3 ml vial Non-Steroidal Antiasthmatic Agents
Leukotriene modifiers:
MA: interrupt synthesis of leukotrienes, which contribute to airflow obstruction in
asthma patients
Leukotriene receptor blockers: Singulair and Accolate
Leukotriene synthesis inhibitor: Zyflo
Ind: NOT for acute therapy; may be used as alternative to low-dose inhaled steroids
or cromones for prophylaxis in mild persistent asthma
AE: headache, dizziness, dyspepsia (indigestion); patients should have liver function
monitored
Montelukast [Singulair]
Adults and children m 15 years: 10 mg tab/d; 6 - 14 years: 5 mg tab/d; 2- 5 years: 4 mg tab/d Zafirlukast [Accolate]
20 mg tab bid; 5 - 11 years: 10 mg tab bid Zileuton [Zyflo]
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