BSTRUCTIVE LUNG DISEASES 2 COPD

CONGENITAL LOBAR OVERINFLATION

Apparent at birth Probably results from hypoplasia of bronchial cartilage Sometimes associated with other congenital cardiac and lung abnormalities

CENTRIACINAR EMPHYSEMA

>95% of emphysema cases The central or proximal parts of the acini, formed by respiratory bronchioles, are affected, distal alveoli are spared More common and usually more severe in the upper lobes, particularly in the apical segments The walls of the emphysematous spaces often contain large amounts of black pigment Inflammation around bronchi and bronchioles is common In severe cases the distal acinus may also be involved, and differentiation from panacinar emphysema becomes difficult Occurs predominantly in heavy smokers, often in association with chronic bronchitis

RESPIRATORY BRONCHIOLUS OF A 17-YEAR-OLD SMOKER

LUNG, 10X. The diameter of a bronchus and the corresponding pulmonary artery are about the same.

SENILE" EMPHYSEMA

Age-related loss of lung mass (atrophy) Affects the entire lung but is often more pronounced in the upper lobes

PATHOGENESIS OF EMPHYSEMA

Alveolar wall destruction results from protease - antiprotease imbalance and oxidant - antioxidant imbalance Chronic inflammation in the lung with neutrophils, macrophages, and CD8+ T-lymphocytes results in the release of leukotriene B4, IL-8, TNF and other mediators Elastase, proteinase 3, and cathepsin from neutrophils and matrix metalloproteinases from neutrophils and macrophages damage the extracellular matrix Any stimulus that increases neutrophils in the lung will increase elastolytic activity (tobacco) Air pollutants and tobacco smoke act by oxidizing alphā-antitrypsin and other antiproteases Inherited α1-antitrypsin deficiency

PANACINAR (PANLOBULAR) EMPHYSEMA

Acini are uniformly enlarged from the level of the respiratory bronchiole to the terminal blind alveoli (The "pan" refers to the entire acinus, not to the entire lung) Occurs more commonly in the lower zones and in the anterior margins of the lung Usually most severe at the bases Associated with α1-antitrypsin (α 1-AT) deficiency

IRREGULAR EMPHYSEMA

Acinus is irregularly involved Almost invariably associated with scarring May be the most common form of emphysema; careful search of most lungs at autopsy shows one or more scars from a healed inflammatory process Foci of irregular emphysema are usually asymptomatic and clinically insignificant

If patients treated with LABA/LAMA/ICS still have exacerbations the following options may be considered:

Add roflumilast. This may be considered in patients with an FEV1 < 50% predicted and chronic bronchitis,13 particularly if they have experienced at least one hospitalization for an exacerbation in the previous year. Add a macrolide. The best available evidence exists for the use of azithromycin. Consideration to the development of resistant organisms should be factored into decision making. Stopping ICS. A reported lack of efficacy, an elevated risk of adverse effects (including pneumonia) and evidence showing no significant harm from withdrawal supports this recommendation

BRONCHIECTASIS

BRONCHIECTASIS DEFINITION: Chronic necrotizing inflammation in bronchial wall leading to destruction of smooth muscle, elastic tissue, and cartilage and resulting in cylindrical or saccular dilatation. ETIOLOGY: Inflammatory: Pneumonia (S. aureus, Klebsiella) Chronic bronchitis Tuberculosis Bronchial obstruction: Foreign body Tumor 3. Genetic: Cystic fibrosis Ciliary dyskinesis (Kartagener syndrome)

KARTAGENER SYNDROME

CLINICAL FEATURES: Primary ciliary dyskinesia Situs inversus Bronchiectasis, sinusitis Infertility INHERITANCE: Autosomal recessive Gene map locus: 9p21-p13, 7p21, 5p15-p14

CYSTIC FIBROSIS

CYSTIC FIBROSIS Incidence: 1 in 3200 live births (Caucasians) Carrier frequency: 1 in 25-30 The most common lethal autosomal recessive disorder affecting Caucasians; much less common in other ethnic groups The cystic fibrosis transmembrane regulator gene (CFTR) is located on chromosome 7 (7q31-32) > 1800 mutations have been identified cAMP-dependent chloride channels (cystic fibrosis transmembrane conductance regulators are defective Epithelial membranes are relatively impermeable to chloride ions Associated with a defect in the secretory process of exocrine glands Clinical manifestations in the lung and pancreas are due to abnormally viscous secretions High level of sodium chloride in the sweat is a consistent and characteristic biochemical abnormality in CF

CAT assessment

Can be used in place of MRC Rates cough, phlegm, chest tightness, shortness of breath walking stairs, ADL's, confidence leaving home, sleep and energy on a 0-5 likert scale.

CHRONIC BRONCHITIS - RECAP

Chronic bronchitis is defined as persistent productive cough for at least 3 consecutive months in at least 2 consecutive years. Cigarette smoking is the most important risk factor; air pollutants also contribute. The dominant pathologic features are mucus hypersecretion and persistent inflammation. Histologic examination demonstrates enlargement of mucus-secreting glands, goblet cell hyperplasia, chronic inflammation, and bronchial wall fibrosis

Chronic Bronchitis

Clinical definition: Present in any patient, who has persistent cough with sputum production for at least 3 months in at least 2 consecutive years in the absence of any other identifiable disease Simple chronic bronchitis: - Productive cough - No airflow obstruction Chronic asthmatic bronchitis: - Hyperreactive airways - Intermittent bronchospasm and wheezing Obstructive chronic bronchitis: - Chronic airflow obstruction - Emphysema

COPD

Clinical features Insidious beginning Takes 30 years to kill (exception: asthma) Progressive dyspnea is the most important symptom Clinical manifestations appear after one third of functioning lung parenchyma is destroyed (exception: asthma) Wheezing, coughing, and expectoration in varying proportions depending on the type of COPD

RESPIRATORY BRONCHIOLITIS (SMALL AIRWAYS DISEASE)

Common in smokers Airways <2-3 mm diameter affected The earliest manifestation of COPD Infection does not play a primary role MECHANISM: Small airways are normally tethered by the elastic recoil of the lung parenchyma Loss of elastic tissue in the walls of alveoli surrounding respiratory bronchioles reduces radial traction Respiratory bronchioles collapse during expiration resulting in functional airflow obstruction despite the absence of mechanical obstruction

Pharmacologic treatment algorithms

Group A All Group A patients should be offered bronchodilator treatment based on its effect on breathlessness. This can be either a short- or a long-acting bronchodilator. This should be continued if symptomatic benefit is documented.

EMPHYSEMA

DEFINITION: Abnormal permanent enlargement of the air spaces distal to the terminal bronchioli accompanied by destruction of their walls ETIOLOGY: Smoking Air pollution Alpha 1-antitrypsin deficiency

DIAGNOSIS OF COPD

DIAGNOSIS OF COPD History and physical examination Chest radiograph or CT Pulmonary function tests: - Slowing of forced expiration is the only reliable and consistently present finding

OUTCOME OF COPD

Depends on the severity of lung damage and the ability to arrest further tissue destruction Emphysematous areas do not revert to normal A destroyed alveolus is gone forever Fibrosis does not go away - Respiratory insufficiency - Pulmonary hypertension - Cor pulmonale - Heart failure - Death most often due to right-sided heart failure or respiratory acidosis and coma

BULLOUS EMPHYSEMA

Descriptive term for large subpleural blebs or bullae (>1 cm in diameter in the distended state) Can occur in any form of emphysema Represents localized accentuations of emphysema Occurs near the apex, sometimes in relation to old scars Rupture of the bullae may give rise to pneumothorax

BRONCHIOLITIS

Diagnosis: Respiratory bronchiolitis. Description: Bronchiolar and peribronchiolar accumulation of pigment-laden macrophages.

COMPENSATORY EMPHYSEMA

Dilation of alveoli but no destruction of septal walls in response to loss of lung substance elsewhere; Results from hyperexpansion of the residual lung following surgical removal of a diseased lung or lobe

Non-Pharmacologic Treatment of OLD

Education and self-management Physical activity Pulmonary rehabilitation programs Exercise training Self-management education End of life and palliative care Nutritional support Vaccination Oxygen therapy

69 yr old male with cough and SOB Mr. B is a 69-year-old man with a h/o HTN, hyperlipidemia, who is here to establish care with you after having moved into the area recently. He comes at his wife's urging because over the last year he has been getting short of breath on their daily walk together. PMH: HTN, Hyperlipidemia Breathing with pursed lips on exhalation Lungs: Somewhat prolonged expiration. Breathing comfortably on RA, no retractions, good air entry, intermittent expiratory wheezes, no crackles or rhonchi. Slight barrel chest He brings in a copy of a spirometry report done just before he moved: FEV1/FVC 0.62, FEV1 55% of predicted, TLC 98% predicted, DLCO 58%, with no significant reversibility with bronchodilator use. He never went back to follow-up on these results due to having moved. DDx?

Emphysema Congestive heart failure Asthma Bronchiectasis Pneumonia Pulmonary embolism Pulmonary vascular disease

EMPHYSEMA MORPHOLOGY:

Enlargement of air spaces Destruction of alveolar walls, alveolar ducts and respiratory bronchioli "Free-floating" islands of tissue Bullae Several subtypes based on the anatomic distribution of changes in the lobule

Diagnosis of emphysema

History and Physical are key! Pulmonary Function Tests are the gold standard for diagnosis and will demonstrate an obstructive pattern Decreased FEV1/FVC ration (<70% predicted) is best indicator FEV1 is a good marker for severity of disease Increased lung volumes (FRC, RV, RV/TLC ratio) may occur due to airway obstruction resulting in air trapping and hyperinflation Decreased diffusing capacity common

Chronic Bronchitis

INCREASED BRONCHIAL MARKINGS IN BOTH LUNGS QUESTIONABLE DENSITIES IN RL ACCENTUATED SEPTAL LINE (ARROW) - FLUID? INFLAMMATION? FIBROSIS?

INTERSTITIAL EMPHYSEMA

INTERSTITIAL EMPHYSEMA Air in the connective tissue stroma of the lung, mediastinum, or subcutaneous tissue Causes: - Alveolar tears - Chest wounds that allows air to be sucked in - Fractured ribs that punctures the lung - Inhalation of irritant gases Patients at risk: - COPD patients: Combination of coughing and bronchiolar obstruction produces sharply increased pressures within the alveolar sacs - Children with whooping cough and bronchitis - Patients with airway obstruction by blood clots or foreign bodies - Artificially ventilated patients - Premature infants and neonates with hyaline membrane disease have a particularly high risk because of their delicate lung structure

BRONCHIOLITIS

Inflammation of the bronchioles that usually occurs in children younger than 2 years and is often caused by the respiratory syncytial virus.

Group B

Initial therapy should consist of a long acting bronchodilator. Long-acting inhaled bronchodilators are superior to short-acting bronchodilators taken as needed i.e., pro re nata (prn) and are therefore recommended. There is no evidence to recommend one class of long-acting bronchodilators over another for initial relief of symptoms in this group of patients. In the individual patient, the choice should depend on the patient's perception of symptom relief. For patients with persistent breathlessness on monotherapy the use of two bronchodilators is recommended. f the addition of a second bronchodilator does not improve symptoms, we suggest the treatment could be stepped down again to a single bronchodilator. Group B patients are likely to have comorbidities that may add to their symptomatology and impact their prognosis, and these possibilities should be investigated.

Group C

Initial therapy should consist of a single long acting bronchodilator. In two head-to head comparisons the tested LAMA was superior to the LABA regarding exacerbation prevention, therefore we recommend starting therapy with a LAMA in this group. Patients with persistent exacerbations may benefit from adding a second long acting bronchodilator (LABA/LAMA) or using a combination of a long acting beta2-agonist and an inhaled corticosteroid (LABA/ICS). As ICS increases the risk for developing pneumonia in some patients, our primary choice is LABA/LAMA.

What is Obstructive Lung Disease?

Lung disease with shortness of breath due to difficulty exhaling all the air from the lungs. Because of damage to the lungs or narrowing of the airways inside the lungs, exhaled air comes out more slowly than normal. At the end of a full exhalation, an abnormally high amount of air may still linger in the lungs.

OBSTRUCTIVE OVERINFLATION:

Lung expands because air is trapped within it Causes: Subtotal obstruction by a tumor or foreign object Mechanisms: - Ball-valve action of the obstructive agent; air enters on inspiration but cannot leave on expiration - Ventilation through collaterals may bring in air from behind the obstruction (pores of Kohn and canals of Lambert) Can be a life-threatening emergency, if the affected portion distends sufficiently to compress the remaining normal lung

Treatment emphysema

Medication Smoking cessation Pulmonary rehabilitation Surgery

CHIEF COMPLAINT: "I'm short of breath; I can't stop coughing and I produce a lot of phlegm, especially in the morning." 62 y/o auto mechanic presents with progressive shortness of breath for the past several days. Began four days ago when "I got a cold." His "cold" consisted of a sore throat, rhinorrhea and myalgia. His job forces him to work in the cold and damp air. At first he just felt tired but later he developed a cough* and shortness of breath. Initially, the cough was dry but within 24 hours of onset, it produced abundant yellow-green sputum. He states, "I cough up a cup of this stuff every day." He didn't think much of the cough because he continually coughs during the winter of each year. His wife states that he "hacks and spits up" every morning when he gets up from bed. He has been treated for high blood pressure, pneumonias and infections of his hands. He has been treated for similar episodes of coughing and shortness of breath during the past two years. He smokes 1-2 packs of cigarettes per day and has done so for the past 35 years (between 35 and 70 pack-year history) Speaks with difficulty, quickly becoming breathless. Cyanosis noted which intensifies during coughing spells. HEENT: use of accessory muscles during respiration. Heart: Soft heart sounds: S2 is split and louder than S1. An S4 is heard best along the left lower sternal border. Abdomen: Round / soft. No BS auscultated. The liver edge is round, slightly tender and palpable 2cm beneath the right costal margin in the mid-clavicular line. Extremities: + pitting edema of the ankles. Differential?

Pulmonary Embolism Pneumonia Emphysema Heart Failure Acute Bronchitis Chronic Bronchitis

TISSUES AFFECTED IN PATIENTS WITH CF

Pulmonary changes cause the most problems Obstruction of the air passages by viscous mucus secretions of submucosal glands and superimposed infections. Bronchiolar distension by thick mucus, associated with marked hyperplasia and hypertrophy of the mucus-secreting cells. Superimposed infections result in severe chronic bronchitis and bronchiectasis and commonly lung abscesses. Most common organisms: Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa. Worst organism: Burkholderia cepacia (an opportunistic pseudomonad) Infection is difficult to treat Associated with fulminant illness ("cepacia syndrome").

PATHOPHYSIOLOGIC FEATURES OF COPD

Reduced flow rate during forced expiration A constant feature in all forms of COPD Increased total lung capacity (in emphysema) Increased compliance = distensibility (in emphysema) Decreased elasticity Increased residual volume Reduced diffusing capacity

Tissue specific cystic fibrosis

SWEAT GLANDS - In CF the concentrations of sodium and chloride ions in the sweat gland are normal, but the duct epithelium is impermeable to chloride ions. - When the sweat moves to the surface, reabsorption of chloride ion through CFTR and the accompanying sodium ion fails to occur resulting in salty sweat High level of sodium chloride in the sweat is a consistent and characteristic diagnostic abnormality in CF. AIRWAYS: - In normal airways chloride ion is secreted into the lumen through cAMP-dependent chloride channels. - In CF patients' airways the impaired transport of chloride from the epithelium into the lumen leads to increased absorption of sodium and water from the airspace to the blood stream leading to low water content in the mucus blanket and abnormally viscous secretions, defective ciliary action, and impaired bronchopulmonary toilet. - Accumulation of viscous secretions predisposes to recurrent infections and eventually destruction of the lungs.

Clinical Presentation Symptoms of emphysema (pink Puffer)

Severe dyspnea minimal cough increased work of breathing decreased air movement prolonged expiration accessory muscle use barrel chest pursed lip breathing weight loss "tripod" sitting hyperresonance

Group D

Starting therapy with a LABA/LAMA combination because: In studies with patient reported outcomes as the primary endpoint LABA/LAMA combinations showed superior results compared to the single substances. If a single bronchodilator is chosen as initial treatment, a LAMA is preferred for exacerbation prevention based on comparison to LABAs A LABA/LAMA combination was superior to a LABA/ICS combination in preventing exacerbations and other patient reported outcomes in Group D patients Group D patients are at higher risk of developing pneumonia when receiving treatment with ICS. n some patients initial therapy with LABA/ICS may be the first choice. These patients may have a history and/or findings suggestive of asthma-COPD overlap. High blood eosinophil counts may also be considered as a parameter to support the use of ICS, although this is still under debate (for details see Chapter 2 and Appendix). In patients who develop further exacerbations on LABA/LAMA therapy we suggest two alternative pathways: Escalation to LABA/LAMA/ICS. Studies are underway comparing the effects of LABA/LAMA vs. LABA/LAMA/ICS for exacerbation prevention. Switch to LABA/ICS. However, there is no evidence that switching from LABA/LAMA to LABA/ICS results in better exacerbation prevention. If LABA/ICS therapy does not positively impact exacerbations/symptoms, a LAMA can be added.

Primary initiating factor is chronic irritation by inhaled substances:

Tobacco smoke Dust (grain, cotton, silica, etc.) Environmental indoor and outdoor air pollution Most frequent in middle-aged men, but both sexes are affected 90% of patients are smokers Most common in heavy smokers regardless of age, sex, occupation, and geography Infection is a secondary, but significant factor: maintains inflammation produces acute exacerbations

The most common causes of OLD

The most common causes: Chronic Obstructive Pulmonary Disease (COPD) Includes emphysema and chronic bronchitis Asthma Bronchiectasis Cystic fibrosis Obstructive lung disease makes it harder to breathe, especially during increased activity or exertion. As the rate of breathing increases, there is less time to breathe all the air out before the next inhalation.

DISTAL ACINAR (PARASEPTAL) EMPHYSEMA

The proximal portion of the acinus is normal, the distal part is predominantly involved More striking adjacent to the pleura, along the lobular connective tissue septa and at the margins of the lobules Occurs adjacent to areas of fibrosis, scarring, or atelectasis Usually more severe in the upper half of the lungs Multiple, continuous, enlarged airspaces from less than 0.5 cm to more than 2.0 cm in diameter, sometimes forming cystlike structures (bullae) Probably underlies many of the cases of spontaneous pneumothorax in young adults

Dyspnea scale (modified MRC)

mMRC grade 0 breathless with strenuous exercise mMRC grade 1 SOB when hurrying on level or walking up a slight hill mMRC grade 2 Walk slower than people of same age on level due to SOB, or have to stop for breath when walking on my own pace on level mMRC grade 3 Stop for breath after walking 100 meters or after a few minutes at level mMRC grade 4 too breathless to leave house or after dressing/undressing

PANACINAR EMPHYSEMA α1 ANTITRYPSIN DEFICIENCY

α1 AT is encoded by codominantly expressed genes in the polymorphic Pi locus on chromosome 14 PiMM (normal) is the most common genotype 0.012% of US population is homozygous for the Z allele, PiZZ, which is associated with markedly decreased serum levels of α1- AT