Manifestation of Novel Social Challenges of the European

Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s Programmes at the University of Pécs and at the University of Debrecen Identification number: TÁMOP-4. 1. 2 -08/1/A-2009 -0011

Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s Programmes at 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

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 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: SO 2, NO 2, O 3, smoking etc. )?

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Age-related changes of the respiratory system 2 • Respiratory muscles start to weaken at around the age of 55, causing a restrictive respiratory disorder. • Chest compliance decreases, 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.

In certain individuals, destruction of the pulmonary elastic fibers leads to a distension of the chest: barrelchest TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Normal Barrel-chest

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 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. • Cardiopulmonal cachexia 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.

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Living with osteoporosis: kyphoscoliosis At age 55 At age 65 At age 75

Age-related abnormal changes in the respiratory system 4 Ventilation and diffusion TÁMOP-4. 1. 2 -08/1/A-2009 -0011 • Eventually aging-associated emphysema develops, 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)

Age-related abnormal changes in the respiratory system 5 Speed of airflow TÁMOP-4. 1. 2 -08/1/A-2009 -0011 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 (FEV 1) decreases regularly by about 20 -30 ml a year Narrowing of the small and bigger airways further enhance the decline in FEV 1. (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 FEV 1.

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Age-related decline in FEV 1 % of FEV 1 value at age 25 years 100 Never smoked or not susceptible to its effects 75 Stopped at 45 50 Smoked regularly and susceptible to its effects 25 Disability Stopped at 65 Death 0 25 50 75 Age (years)

Age-related abnormal changes in the respiratory system 6 Respiratory regulation TÁMOP-4. 1. 2 -08/1/A-2009 -0011 • Responsiveness of the respiratory center to hypercapnia and hypoxia-induced (peripheral chemoreceptor) stimuli is steadily decreasing • There is a steady decrease of 0. 3% p. O 2 per year, due to the impairment of the respiratory regulation (further decrease is due to an impaired 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.

Age-related abnormal changes in the respiratory system 7 Defence mechanisms TÁMOP-4. 1. 2 -08/1/A-2009 -0011 • 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: Ig. G and Ig. A do not change with age, but Ig. M decreases • Cellular immunity: decreases with age (type IV late hypersensitivity reaction is down above 60 years of age)

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 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: 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 tuberculotic reinfection may develop! - Signs include cough, weight loss, night-time sweating, subfebrility

TÁMOP-4. 1. 2 -08/1/A-2009 -0011 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.

Age-related abnormal changes in the respiratory system 10 Lung cancer in the elderly TÁMOP-4. 1. 2 -08/1/A-2009 -0011 • 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.

Age-related abnormal changes in the respiratory system 11 Pulmonary fibrosis TÁMOP-4. 1. 2 -08/1/A-2009 -0011 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)

Age-related abnormal changes in the respiratory system 12 Pulmonary fibrosis TÁMOP-4. 1. 2 -08/1/A-2009 -0011 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.

Age-related abnormal changes in the respiratory system 13 Sleep apnea syndrome TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Definition Recurrent apneic/hypopneic prediods (>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 • aging risk above 65 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)

Age-related abnormal changes in the respiratory system 14 Sleep apnea syndrome TÁMOP-4. 1. 2 -08/1/A-2009 -0011 Symptoms loud snoring (peripheral obstructive form, in a dorsal position), frequent waking daytime 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)

Age-related abnormal changes in the respiratory system 15 Pulmonary embolism in the elderly TÁMOP-4. 1. 2 -08/1/A-2009 -0011 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 • polycythaemia vera • 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

Age-related abnormal changes in the respiratory system 16 Pulmonary embolism in the elderly TÁMOP-4. 1. 2 -08/1/A-2009 -0011 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

Age-related abnormal changes in the respiratory system 17 Respiratory failure TÁMOP-4. 1. 2 -08/1/A-2009 -0011 • Prevalence is more than 10 % in adults • Incidence of acute respiratory failure increases from 60 -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 (p. O 2< 60 Hgmm), global respiratory failure with hypoxia and hypercapnia (p. O 2< 60 Hgmm, p. CO 2>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.