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Obstructive Lung Diseases

Chronic obstructive pulmonary disease

• A disorder characterized by abnormal tests of expiratory flow that do not change markedly over periods of several months duration (intended to distinguish COPD from asthma).

• Bronchial hyperreactivity may be present in patients with COPD as measured by an improvement in airflow following the inhalation of beta-adrenergic agents or worsening after inhalation of methacholine or histamine.

Three disorders are incorporated into COPD:

Emphysema

A condition of the lung characterized by abnormal permanent enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls, and without obvious fibrosis

Chronic bronchitis

Chronic or recurrent excess mucus secretion into the bronchial tree occurring on most days for at least three months/year for at least two successive years

Peripheral airways disease

Inflammation of the terminal and respiratory bronchioles, fibrosis of the airway walls, and goblet cell metaplasia. These changes may represent early or preclinical COPD:

• Affects 15,000,000 Americans

• 4th leading cause of death in the US Mortality rate 10 years after diagnosis is 50%

Emphysema

A pathological diagnosis supported by PFTs that characteristically show airflow obstruction, air trapping, and reduced DLCO, thus the diagnosis is made on clinical grounds

Pathogenesis of emphysema

• Intratracheal elastase causes development of experimental emphysema (Gross, 1965)

• a₁-antitrypsin deficiency is associated with development of early emphysema Protease-antiprotease theory, Janoff

• Diagnosis of al-protease inhibitor deficiency:

    Young individual (<40 years) with progressive dyspnea, severe obstruction on

    PFrs, hyperlucent lungs on CXR especially in lower lung fields

Chronic bronchitis

Can occur with or without airflow obstruction (the latter is termed simple chronic bronchitis)

Bronchiectasis

Associated conditions

Infection- responsible for most cases of bronchiectasis Bronchial obstruction

Primary ciliary dyskinesia Cystic fibrosis

Allergic bronchopulmonary aspergillosis Immunodeficiency

a1-antitrypsin inhibitor deficiency Unilateral hyperlucent lung

Bronchopulmonary sequestration Tracheobronchomegaly

Yellow-nails syndrome

Problems in COPD

• Increased resistance to airflow due to narrowing of airways and increased collapsibility of airways

Treatment of COPD

• Indices of clinical improvement

Improvement in spirometric indices

FEV₁ or VC improve 0.20 L

Improvement in gas exchange indices

Sympathomimetic Agents

• Potential for inducing hypokalemia must be recognized

• Anticholinergic agents

• Ipatroprium and nebulized atropine have been reported to produce greater bronchodilation than conventional doses of -agonists

• Maximal doses of -agonists probably produce the same degree of bronchodilation

• Ipratropium and a -agonists are equally effective in the treatment of acute exacerbations of COPD

• Neither medication potentiates the action of the other

• Because of its slower onset and longer duration of action it is more suitable for use on a regular basis rather than PRN

Theophylline

• Administration at night decreases overnight decline in FEV₁ and morning respiratory symptoms

• May improve respiratory muscle function, mucociliary clearance, central ventilatory drive, and possibly airway inflammation

• Maintain serum concentration of 5-15 ug/mL

Corticosteroids

• Some patients may benefit- it is not possible to predict who a priori

• A closely monitored trial of therapy should be considered in patients who have continuing

symptoms or severe airflow limitation despite maximal therapy with other agents

• Long-term treatment should be prescribed only for patients with documented improvement in airflow or exercise performance and in the lowest possible dose

• Inhaled steroid therapy may be beneficial in patients with COPD

Lung reduction surgery

20 patients, avg FEV] 0.77 L (25% predicted), 3 with PaCO₂ > 50 mm Hg Median stemotomy, removal of 20-30% of each lung (poorly emptying after anesthesia bag inflation)

No early (6 months) morbidity and mortality 82% improvement in FEV1 39% reduction in RV

Improvement in 6 minute walk, quality of life questionnaire scores

• Sciurba et al, N Engl J Med, 1996

20 patients, avg FEV1 0.87 L (32% predicted)

3-6 months after surgery (thoracoscopy with YAG laser or sternotomy):

FEV₁ increases 28%

RV decreases 16%

TLC decreases 6%

Elastic recoil at TLC increases 14%

Lung Transplantation

Living-donor lobar lung transplantation

• Starnes et al, J Thorac Cardiovasc Surg 1996; 112:1284-1291

USC experience, 38 living donor double-lower lobe transplants in 27 adult and 10 pediatric patients (mostly cystic fibrosis)

2000 patients on transplant list- most die waiting transplant

End-stage patients, 6 on ventilators, mean PaCO₂ = 69 mm Hg, mean FEV1 = 19% One-year survival 68% (national survival = 73%), good functional status in survivors

In 76 donors, 3 with re-ops, 3 with post-pericardiotomy syndrome

 

Asthma

"...a disease characterized by an increased responsiveness of the trachea and bronchi to various stimuli manifested by widespread narrowing of the airways that changes in severity either spontaneously or as the result of therapy."

• Prevalence- 5% of population

• Basic characteristics

Airway obstruction that is at least partially reversible either spontaneously or with treatment 

Airway hyperresponsiveness to a variety of stimuli 

Airway inflammation 

Risk factors for asthma 

Allergens and atopy 

House dust mites 

Respiratory infections 

Diet

Genetic factors, including race and gender

Passive smoking

• Functional consequences of airway inflammation

Airway hyperresponsiveness

Peak flow variability

Airflow limitation

• Drugs used to treat asthma

Aerosolized corticosteroids (beclomethasone, triamcinolone, flunisolide, budesonide, fluticasone)

First-line drugs for chronic asthma

Proper technique in using MDIs essential- ? need for spacers

Side effects: oral candidiasis, dysphonia

Suppression of hypothalamic-pituitary-adrenal axis with high doses

Can substitute for systemic steroids when high doses (1500-2000 ug/day) are given 

Problems with compliance and expense 

Systemic corticosteroids Cromolyn and nedocromil 

Theophyline Anticholinergic agents Zafirlukast, zileuton, montelukast

Other drugs (methotrexate, troleandomycin, Au salts)

Therapy guidelines

National Asthma Education Program Expert Panel Report 2

National Asthma Education Program - NHLBI, 1997

Mild intermittent: 

wheeze/cough/dyspnea up to BIW, brief Sx with activity, nocturnal Sx <2 times/month Rx: agonist via MDI pre exposure or q3-4 hr PRN

Mild persistent:

Sx >2/week but < I/day, nocturnal Sx >2/month

Rx: Inhaled corticosteroids or cromolyn or nedocromil, b2 agonist via MDI PRN to QID. If necessary add theophylline, zafirlukast, zileuton, or montelukast

Moderate persistent:

Daily Sx, daily use of b2 agonist, nocturnal Sx >1/week

Rx: Inhaled corticosteroids (medium doses), b2 agonist via MDI PRN to QID, salmeterol, sustained release theophylline, long acting oral b2 agonist

Severe persistent:

Continuous Sx, limited activity level, frequent exacerbations, frequent nocturnal Sx 

Rx: Inhaled corticosteroids (high doses), salmeterol, sustained release theophylline, long acting oral [32 agonist, b2 agonist via MDI [32 agonist via MDI PRN to QID. Systemic corticosteroids (up to 60 mg prednisone daily)

Inhaled steroids and the risk of hospitalization for asthma

(Donahue et al, JAMA 1997; 277: 887-891)

Retrospective cohort study of HMO members in eastern Massachusetts

16,941 people with Dx of asthma

742 hospitalizations for asthma (4.4% of sample)

Relative risk of hospitalization 0.5 in patients prescribed inhaled steroids Increasing 15 agonist use associated with increase risk of hospitalization (RR = 4.3 c/w no b2 agonis0

Inhaled steroids reduced risk in all age groups

Effect of Long-Term Treatment with Salmeterol on Asthma Control

(Wilding et al, BMJ 1997; 314: 1441-1446)

Determine the effect of adding salmeterol 50 ug BID to current Rx in pts with mild to moderate asthma requiring > 400 gg beclomethasone daily

Double blind, randomized crossover study, 101 patients, 6 months per crossover period

Very tight control, vary inhaled steroids depending on PEFR

Salmeterol use associated with:

17% reduction in steroid use

Improved PEFR, FEV₁ symptom score

Decreased bronchial hyper-responsiveness to methacholine

No tachyphylaxis to acute administration of albuterol

Oral Montelukast, Inhaled Beclomethasone, and Placebo for Chronic Asthma

(Malmstrom et al, Ann Int Med 1999; 130: 487-495

895 patients with FEV₁ 50-85% predicted, mild intermittent or mild to moderate persistent asthma Rx'ed with theophylline or PRN b2 agonists

12 week treatment period: montelukast 10 mg OD, beclomethasone MDI 200 ug BID, or placebo

FEV₁ change from baseline: 13% beclomethasone, 7% montelukast, 1% placebo Montelukast had faster onset (1 day vs 1 week) and greater initial effect

No Churg-Strauss syndrome seen, small decrease in eosinophilia noted

 

Acute asthma

• Lung mechanics

Reduction in expiratory flow due to narrowing of airway caliber in large and small airways

Increase in lung volumes (RV, FRC, TLC) due to closure of small airways in expiration and "breath stacking"

• Gas exchange

Hypoxemia secondary to development of low V/Q regions

Increased Vd/vt (wasted ventilation) due to development of high regions (overventilation

of regions of lung with less severe obstruction to airflow)

Arterial PCO₂ initially <40 mm Hg, then "pseudo-normalization," then >40 mm Hg as severity of airflow obstruction increases and respiratory muscle fatigue develops

• Hemodynamics

Development of pulsus paradoxus

Occasionally RV strain and p-pulmonale on EKG