Changes of the respiratory system, frequent diseases

1. Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011

2. Manifestation of Novel Social Challenges of the European Unionin the Teaching Material ofMedical Biotechnology Master’s Programmesat the University of Pécs and at the University of Debrecen Identification number: TÁMOP-4.1.2-08/1/A-2009-0011 Márta Balaskó and Miklós Székely Molecular and Clinical Basics of Gerontology – Lecture 10 Changes of the respiratory system, frequent diseases

3. Age-related changes of the respiratory system 1 • In the course of aging the elements of the respiratory system (chest, lungs, airways) develop important morphological alterations. • Pulmonary functions: ventilation, gas exchange, defense mechanisms, all change with age! • How much of this is intrinsic pathophysiological (exhaustion of adaptation mechanisms) and how much is a consequence of environmental factors (air pollution: SO2, NO2, O3, smoking etc.)?

4. Age-related changes of the respiratory system 2 • Respiratory muscles start to weakenat around the age of 55, causing a restrictive respiratory disorder. • Chest compliance decreases, rib cartilage is turned into bone, enhanced dorsal kyphoscoliosis, aggravating the restrictive respiratory disorders further. • Elastic recoil of the lungs decreases, lung compliance increases (because of the damage to the elastic fibers) leading to emphysema. In certain individuals the weakness of the elastic fibers and the diminished inward pull on the chest lead the expansion of the chest and to the development of barrel chest. • All the above factors lead to an increase in total lung capacity (TLC), increasing functional residual capacity (FRC hyperinflation) and the value of residual volume (RV). Alterations in airways also promote these changes.

5. In certain individuals, destruction of the pulmonary elastic fibers leads to a distension of the chest: barrel-chest Normal Barrel-chest

6. Age-related abnormal changes in the respiratory system 3 • Osteoporosis and vertebral compression may lead to excessive kyphoscoliosis– enhanced dorsal kyphosis, restrictive chest disorder. • Special complications • In severe osteoporosis cough may lead to rib fracture. • In severe emphysema of the elderly cough may lead to acute pneumothorax via rupture of one of the thin distended bullae. • Cardiopulmonalcachexia may develop. In severe pulmonary diseases food intake may induce such a severe dyspnea, that patients would rather not eat. Deficiency of energy balance may also be aggravated by sustained high metabolic rate induced by inflammation, and high energy demand of increased work of breathing.

7. Living with osteoporosis: kyphoscoliosis Atage 65 Atage 75 Atage 55

8. Age-related abnormal changes in the respiratory system 4 • Ventilation and diffusion • Eventually aging-associated emphysema develops, due to a decrease of the elastic fiber network (that would normally protect the airways from collapsing in expiration by anchoring them to nearby morphological units), the small airways collapse during expiration due to the positive pressure in the lungs. • In case of airway inflammation small airways grow narrower (due to inflammatory edema, infiltration, increased mucus production, increased bronchoconstriction). Abnormalities of the small airways lead to uneven alveolar ventilation, V/Q mismatch • Obstruction of the small airways increases the functional shunt circulation. Damage of the interveolar capillaries increase the functional deadspace. • Steadily decreasing diffusion surface leads to an annual decrease of 0.5% in diffusion capacity (DLCO)

9. Age-related abnormal changes in the respiratory system 5Speed of airflow • Dynamic respiratory parameters that take into consideration the speed of airflow, e.g. forced vital capacity (FVC) decrease with age. Forced expiratory volume in 1 second (FEV1) decreases regularly by about 20-30 ml a year. • Narrowing of the small and bigger airways further enhance the decline in FEV1. (Diameter of small airways with a narrower initial lumen tend to decrease further due to a positive pressure during expiration.) Smoking-induced airway inflammation may also cause disproportionate decrease in FEV1.

10. Age-relateddeclinein FEV1 100 Never smoked or not susceptible to its effects 75 Stopped at 45 50 % of FEV1 value at age 25 years Smoked regularly and susceptible to its effects 25 Disability Stopped at 65 Death 0 25 50 75 Age (years)

11. Age-related abnormal changes in the respiratory system 6 Respiratory regulation • Responsiveness of the respiratory center to hypercapniaand hypoxia-induced (peripheral chemoreceptor) stimuli is steadily decreasing • There is a steady decrease of 0.3% pO2 per year, due to the impairment of the respiratory regulation (further decrease is due to animpaired performance of the lungs) • By 70 years of age there is a 40-50% decrease in the sensitivity. (Old people tolerate rather than defend themselves of hypoxic states, e.g. high altitude, pneumonia, COPD.) They develop respiratory failure sooner.

12. Age-related abnormal changes in the respiratory system 7 • Defence mechanisms • Clearance: the intensity of the mucociliary transport shows a negative correlation with age. • Loss of the cough-reflex that also serves the clearance and defense of the airways. • Humoral immunity:IgG and IgA do not change with age, but IgM decreases • Cellular immunity: decreases with age (type IV late hypersensitivity reaction is down above 60 years of age)

13. Age-related abnormal changes in the respiratory system 8 • The prevalence of airway infections is enhanced in the elderly. Pneumonia develops frequently. • Diagnosis is difficult: • - Due to the weakened immune system many non-specific infectious agents are seen, symptoms are also non-characteristic. Instead of fever, cough, breathing-associated pain observed in the young , confusion or incontinence maybe the only sign of pneumonia. • - In hypovolemic patients chest X-rax may be false negative. • - Due to the weakened immune system endogenic exacerbations or exogenous reinfections are common. • In the elderly, endogenous tuberculoticreinfection may develop! • - Signs include cough, weight loss, night-time sweating, subfebrility

14. Age-related abnormal changes in the respiratory system 9 • Prevalence of chronic obstructive lung diseases (COPD) increases in the elderly, its progression is enhanced in this age-group. (Etiological factors of COPD, smoking or occupational smoke and dust exposure act for a longer time and cause more severe abnormalities.) • Symptoms and clinical findings of patient with (previous diagnosis of) bronchial asthma and COPD differ less and less with aging. (Airway obstruction of older asthmatic patients is not as reversible as it used to be.) • In smokers the prevalence of COPD is 5-7-times higher. • In smokers mortality of COPD is also 7-times higher. • The best way to ameliorate the progression of COPD is by cessation of smoking.

15. Age-related abnormal changes in the respiratory system 10 • Lung cancer in the elderly • Mean age of patients with lung cancer is 70 years. Only 3 % of them are below the age of 45 years. • Smoking plays a primary role in the etiology. (In male smokers the risk of developing lung cancer is 22-times, in female smokers 12-times (due to lower exposure) higher than that of non-smokers. Smoking is responsible for more than 80% of lung cancer mortality.) • Treatment is not efficient, 60% of patients die within 1 year, 75% within 2 years of diagnosis. • The best prevention is being a non-smoker and avoidance of cigarette (cigar, etc.) smoke. • In Hungary, lung cancer present a significant public health problem. We are the first in the world in male lung cancer mortality. Lung cancer is the most frequent malignant tumor in men, the second most frequent among women.

16. Age-related abnormal changes in the respiratory system 11 Pulmonary fibrosis • Definition • Accumulation of connective tissue in the lungs (fibrosis), because of tissue damage/inflammatory processes. • Due to the destruction of the pulmonary parenchyma, respiratory /diffusion surface decreases. • Capillary diameter is diminished, pulmonary pressure rises. • Thickening of the alveolocapillary membrane develops. • As a result, diffusion disorder, in severe cases even alveolar hypoventilation is seen. • Causes • medications: e.g. amiodarone, bleomycin, cyclophosphamide, nitrofurantoin, methotrexate • irradiation • autoimmune alveolitis(in the elderly autoimmune disorders are common) • TBC, sarcoidosis, silicosis, hemochromatosis, poisoning e.g. paraquat • It may also be a consequence of acute respiratory distress syndrome (ARDS)

17. Age-related abnormal changes in the respiratory system 12 Pulmonary fibrosis • Symptoms, complications • Elastic resistance increases, inspiration requires an effort. Restrictive ventilatory disorder is observed. • Superficial, frequent breathing is characteristically seen that leads to the increase in dead space ventilation. • Airflow is diminished, consequently the risk of airway infections, pneumonia and even lung cancer is enhanced. • Respiratory failure frequently develops. Diffusion disorder itself leads to partial, alveolar hypoventilation results in global respiratory failure. • Treatment • Treatment of the underlying disease may slow or stop the progression of fibrosis. • Anti-inflammatory drugs (corticosteroids), certain cytostatic drugs may suppress inflammation and thus delay the progression of pulmonary fibrosis.

18. Age-related abnormal changes in the respiratory system 13 Sleep apnea syndrome • Definition • Recurrent apneic/hypopneicprediods (>10 sec each, >10/hour, >30/night) during sleep at night. • Types • Central (C): sensitivity of the respiratory centre is diminished • Peripheral obstructive (P): collapse of distended, enlarged pharyngeal tissues (snoring), nasal conchae, enlarged tongue may cause obstruction • Etiology • agingrisk above65 years 2-3-times higher (C, P) • stroke, brain tumors (C) • alcohol, tranquillizers (C, P) • atrial fibrillation, congestive heart failure(C), very frequent in the elderly! • obesity, fat accumulation in pharyngeal tissues (P) • male gender 2-times increased risk (P) • menopause (P) • short, thick neck (>43 cm) (P) • familial appearance(P) • prolonged sitting position(P)

19. Age-related abnormal changes in the respiratory system 14 Sleep apnea syndrome • Symptoms • loud snoring (peripheral obstructive form, in a dorsal position), frequent waking day-time somnolence, exhaustion, increased risk for accidents • Consequences • many occasions of respiratory failure of short duration at night • treatment-refractory systemic hypertension, pulmonary hypertension • tendency to develop congestive heart failure, with increased risk for pulmonary edema • morning headache • sleepiness, daytime somnolence, (car)accidents • increased risk for dementia and cognitive disorders • alterations of personality, irritability, aggression • Treatment • reduction of body weight • sleeping on one side (not on the back) • plastic surgery of pharyngeal tissues, nasal conchae • CPAP (continuous positive airway pressure • BI-PAP (variable/bilevel positive airway pressure)

20. Age-related abnormal changes in the respiratory system 15 Pulmonary embolism in the elderly • Definition • Embolism obstructing smaller or larger pulmonary arteries • Causes (in the elderly) • deep venous thrombosis (e.g. from the lower limb or pelvic region) • immobilization • trauma, fractures, surgical fracture treatments (in the latter fat embolization may also develop) • varicosity • compensatory polyglobulia induced by hypoxic states (COPD, pneumonia) • hemoconcentration associated with frequent hypovolemias • obesity • polycythaemiavera • hereditary thrombophilias • Deep venous thrombosis is common in the elderly : at 45 years prevalence is 1:10,000, by the age of 60 years 1:100, mean prevalence is 1:1000

21. Age-related abnormal changes in the respiratory system 16 Pulmonary embolism in the elderly • Symptoms (non-specific) • dyspnea, hemoptysis (blood in sputum), respiration-associated (sharp, pleural) chest pain confusion, collapse, tachycardia • Diagnosis • In about 30% of the cases, it is not diagnosed. This ration is higher in the elderly. • Signs of enhanced coagulation and fibrinolysis (fibrin degradation products, D-dimer) • CT • Lung scintigraphy • pulmonary angiography • Doppler ultrasound (venous) • Phlebography • Treatment • Fibrinolysis

22. Age-related abnormal changes in the respiratory system 17 Respiratory failure • Prevalence is more than 10 % in adults • Incidence of acute respiratory failure increases from60-80/100,000 at 45 years to 500/100,000 at around 65 years of age to reach about 750/100,000 above 75 years. • Partial respiratory failure is associated with hypoxia(pO2< 60 Hgmm), global respiratory failure with hypoxia and hypercapnia (pO2< 60 Hgmm, pCO2>50 Hgmm). • Typical causes of partial respiratory failure include mild-moderate V/Q mismatch, dissusion disorders, high altitude. Those of global respiratory failure include alveolar hypoventilation e.g. COPD. • In severe cases the elderly also require home oxygen therapy.A dose of 1-2 L/h, 12-14 h/day increases survival.