COPD

SS Visser, PulmonologyInternal Medicine

UP

Chronic Obstructive pulmonary Disease

Two distinct processes are involved, most often in combination.Chronic Bronchitis – dx on historyEmphysema – dx previously on histology, nowadays clinically (good clinical-pathologic-radiologic correlation)

Def: Chronic Bronchitis

Excessive tracheobronchial mucus production sufficient to cause cough with expectoration for most days of at least 3 months of the year for 2 consecutive years.Classification:

1. Simple chronic bronchitis2. Chronic mucopurulent bronchitis3. Chronic bronchitis with obstruction4. Chronic bronchitis with obstruction and airway

hyperreactivity.

Def: Emphysema

Permanent abnormal distention of air spaces distal to the terminal bronchiole with destruction of alveolar septa (containing alveolar capillaries) and attachments to the bronchial walls.Classification:

1. Centriacinar ( centrilobular) emphysema2. Panacinar emphysema3. Paraseptal emphysema4. Senile emphysema

Def: COPD

Chronic obstruction to airflow due to chronic bronchitis and/or emphysema.Degree of obstruction may be less when the patient is free from respiratory infection and may improve with bronchodilator drugsSignificant obstruction is always present

Epidemiology of COPD

30% of smokers develop COPD20% of adult males have COPD15% of COPD patients are severely symptomatic4 th leading cause of death (USA)Mortality rate still rising↑prevalence in low birth weight and low socioeconomic status

Pathogenesis:Effects of Smoking -1

Oxidative stress: O2-, OH-,H2O2, HOCl, source of Fe2+-

catalizes production of OH- by neutrophils, eosinophils, alveolar macrophages, tar contains NO and induces iNOS→toxic peroxynitritesElastin breakdown- neutrophil elastases, α-1-AT and metalloproteinase inhibitors inactivated by smoke, oxidants, activated neutrophilsChemoattractant, upregulation of adhesion molecules-neutrophil sequestration in lungs↑expression of pro-inflammatory mediators: IL-8, NF-κB →recruitment of N, B, E and T lymphocytes

Effects of smoking -2

↑ levels of myeloperoxidase and eosinophilic cationic protein → bronchoconstriction↑ levels of TGF-β (transforming growth factor) →fibrogenesisLipid peroxidation and DNA damage →point mutations 0f the p53 gene locus →lung cancer↓ ciliary function, ↑ airway resistance (vagal-mediated smooth muscle contraction)Hypertrophy and hyperplasia of mucus secreting glands

Pathogenesis-3

Air pollution-exacerbations of CB related to heavy pollution with SO2 and NO2Occupation-exposure to organic and inorganic dust or noxious gases →accelerated decline in lung functionInfection-even mild viral respiratory infections ( rhino virus) may be a major factor associated with etiology as well as progression of disease, severe viral pneumonia early in life may lead to COPDGenetic factors: - α-1-antitrypsin deficiency PIZZ, PISZ, PI00 (PI null null), ↑ susceptibility to effects of smoking

Pathophysiology

Air trapping- RV and FRC elevatedHyperinflation –TLC elevated

↓ elastic recoil pressure → dynamic collapse of airways during expiration →ineffective cough mechanism and pursed lips breathing (emphysema) ↑ compliance (emphysema)↑ airway resistanceProlonged forced expiratory time (N=<6 seconds)

Pathology: CB

Hypertrophy of mucus-producing glands in submucosa of large cartilaginous airwaysGoblet cell hyperplasia, mucosal and submucosal inflammatory cell infiltrate, oedema, peribronchial fibrosis, intraluminal mucus plugs and increased smooth muscle in small airwaysThe major site of airflow obstruction is in the small airways and the inflammatory infiltrate consists of neutrophils (in asthma eosinophils)

Pathology : Emphysema

↑in number and size of alveolar fenestrae →eventual destruction of alveolar septa and their attachments to terminal and respiratory bronchioles →distention of alveolar spaces

1. Centriacinar E- respiratory bronchioles (central) affected2. Panacinar E- central and peripheral portions of acinus

affected3. Senile E- alveoli and alveolar ducts enlarge (> 50 Y)4. Periacinar/paraseptal E- distention of alveolar spaces

adjacent to septal and pleural surfaces

Physical signs of COPD

Ronchi- in early disease present on forced expiration, later present in inspiration and expirationProlonged forced expiratory time (> 6 seconds)Hyperinflation: ↓ cardiac dullness, liver dullness displaced downwards, ↑ A-P chest diameter, ↓ heart and breath sounds, Hoover signInspiratory crepitations (lung bases)Pursed lips breathing ( ↓ dynamic airway collapse)Use accessory respiratory musclesSigns of cor pulmonale and PHT

Emphysema:ChronicBronchitis

Emphysema = pink puffer

Age (Dx) 60 + yRest dyspnea mild-modExer dyspnea severeCough ±Sputum scanty, mucoidResp infect less oftenResp failure terminalCor pulmonale terminal

Chronic Bronchitis = bluebloater50 ± ynonemoderateprominentlarge volume, purulentoftenrepeatedlycommon

Emphysema:Chronic Bronchitis

PHT (rest) 0-mild(exer) moderate

Build Asthenic, cachecticHematocrit 35-45Breath pattern use

accessoryResp musclesSleep pattern NormalXRC Hyperinflation

Bullae

Mild-moderatesevereobese, cyanosed50-55do not use accessory resp

musclessleep apnea↑ bronchovascular markings

Emphysema:Chronic Bronchitis

Blood gas:PaO2 ± 65 mm HgPaCO2 35-40Elastic recoil ↓AW resistance N-↑Diffusion Cap ↓FEV1 ↓ ↓BD response Poor

45-6050-60Normal↑N- ↓↓Better but < 12% and 200ml

Treatment: Goals of management -1

Recognition of disease (early Dx and staging)Smoking cessation (secondary prevention)Improvement of breathlessness (Rx of airflow obstruction-bronchodilator drugs)

1.Methylxanthines2.B2adrenergic agonists3.Anticholinergics- BD of choice in COPD

Respiratory infections –AB when ↑sputum volume, purulence, exacerbation of COPD; Influenza and streptococcus pneumoniae vaccination

Treatment -2

Bronchopulmonary drainage and postural drainage (physiotherapy) for patients with CBOxygen therapy for patients with hypoxia (PaO2<55 mmHg, SaO2 <88% ) and erythrocytosis (Hematocrit>55)Pulmonary rehabilitation and education ( improving quality of life)- exercise program and improved nutritionPrevention and treatment of complications (cor pulmonale) and limitation of disease progression

Treatment -3

Glucocorticoids –only 10% of COPD patients show subjective benefit and improved lung function (FeV1 increase of 20% or more) on systemic GCs. Inhaled GCs may ↓ severity of exacerbations and need for hospitalisation. Benefit of 10-14 day trial of 30-40mg prednisone for Stage III COPD patients remain to be proven.Lung volume reduction surgeryTransplantation

Airway Diseases - COPD

SmokingHyperinflationAirway collapseRespiratory infectionBronchospasmAllergyInflammation

Airway Diseases : Asthma

AllergyInflammationBronchospasmHyperinflationRespiratory infection

AirwayDiseases:Bronchiectasis

Respiratory infectionHyperinflationBronchospasmInflammationAllergy