Lecture note bronchial asthma,copd, phtn.ppt

Discusses on bronchial asthma, copd pneumonia, ild and pulmonary hypertension

1. Lecture note R espiratory medicine for clinical I students Yekatit 12 hospital medical college Dr.Tadele Sahlemariam (MD,MBA, assistant professor of internal medicine) O ctober 01 , 2025

2. Objectives Main objective Discuss approach to respiratory disorders.

3. Specific objectives At the end of this session students will be able to: Identify and describe the major types of respiratory disorders. Explain the pathophysiological mechanisms underlying respiratory disorders. Discuss the risk factors associated with various respiratory disorder. Summarize the clinical manifestations and symptoms of common respiratory disorders. Interpret diagnostic tests (e.g., chest X-rays) used in the assessment of respiratory disorders. Demonstrate the ability to formulate a basic management plan .

4. Specific objectives Evaluate the effectiveness of different treatment options based on current evidence and guidelines. Discuss the implications of respiratory disorders on public health and the importance of prevention strategies.

5. Contents Introduction to respiratory disorders and approach to the patient with disease of the respiratory system. Diagnostic Procedures in Respiratory Disease. Diseases of the Respiratory System

6. Introduction The majority of diseases of the respiratory system fall into one of three major categories: Obstructive Restrictive Vascular diseases.

7. Harrison’s principles of internal medicine, 21 st ed.

8. HISTORY Dyspnea and Cough are the cardinal symptoms of respiratory disease. Severity of dyspnea? Tempo of onset and the duration? What exacerbates and relieves the symptoms? Additional symptoms(chest pain, wheeze, fever etc.) Additional history?

9. Physical Examination Respiratory and other systemic examination Diagnostic investigations

10. Diagnostic Procedures in Respiratory Disease

11. Diagnostic procedures in respiratory disease encompass a wide array of invasive and noninvasive modalities.

12. BEDSIDE PLEURAL PROCEDURES Thoracentesis https ://youtu.be/QubaJaH_THc Enclosed pleural biopsy https://youtu.be/pw6vGz_nMvc

13. THORACIC SURGICAL PROCEDURES Thoracoscopy and thoracotomy Mediastinoscopy and mediastinotomy

14. BRONCHOSCOPY Bronchoalveolar Lavage The gold standard method for obtaining respiratory secretions for hematologic,biochemical , microbiological, and/or cytologic analyses . Brushing and Endobronchial Biopsy Transbronchial Biopsy Including Cryobiopsy Transbronchial Needle Aspiration Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration. Guided Peripheral Bronchoscopy Robotic Bronchoscopy

15. Imaging has revolutionized the practice of medicine. x-ray , CT, MRI, and positron emission tomography (PET)

16. MISCELLANEOUS TESTING Sputum examination Exhaled breath condensate Sweat testing ALLERGY TESTING

17. Diseases of the Respiratory System

18. Asthma Asthma is a disease characterized by episodic airway obstruction and airway hyper-responsiveness usually accompanied by airway inflammation . In most cases, the airway obstruction is reversible , but in a subset of asthmatics, a component of the obstruction may become irreversible . Airway inflammation is Eosinophilic (in a large proportion of patients), differing types (some patients) no obvious evidence of airway inflammation(in some cases).

19. “ Asthma : is a heterogeneous disease, usually characterized by chronic airway inflammation. It is defined by the history of respiratory symptoms, such as wheeze, shortness of breath, chest tightness and cough, that vary over time and in intensity , together with variable expiratory airflow limitation .” GINA 2024 Update Global Strategy for Asthma Management and Prevention

20. MANIFESTATIONS Asthma most frequently presents as episodic shortness of breath,wheezing , and cough , which can occur in relation to triggers but may also occur spontaneously. These symptoms can occur in combination or separately. Other symptoms can include chest tightness and/or mucus production . These symptoms can resolve spontaneously or with therapy . In some patients, wheezing and/or dyspnea can be persistent. Episodes of acute bronchospasm, known as exacerbations, may be severe enough to require emergency medical care or hospitalization and may result in death.

21. Asthma phenotypes Allergic asthma Non-allergic asthma Cough variant asthma and cough predominant asthma Adult-onset (late-onset) asthma Asthma with persistent airflow limitation Asthma with obesity

22. Asthma is the most common chronic disease associated with significant morbidity and mortality. ~241 million people affected globally . ~ 4.3% prevalence worldwide. Reduction in mortality has been attributed to increased use of inhaled corticosteroids .

23. Asthma development pathway.

24. Pathophysiology---Asthma Mechanisms leading to acute and chronic airway obstruction 1- Airway Hyper-responsiveness : Is a hallmark of asthma. It is defined as “ an acute narrowing response of the airways in reaction to agents that do not elicit airway responses in non-affected individuals or an excess narrowing response to inhaled agents as compared to that which would occur in non-affected individuals ”.

25. NB:A major therapeutic objective in asthma is to decrease the degree of airway hyper-responsiveness.

26. 2-Inflammatory Cells While airway inflammation can be precipitated by acute exposure to inhalants, most asthmatics have evidence of chronic inflammation in the airways. Most commonly, this inflammation is eosinophilic in nature. In some patients, neutrophilic inflammation may be predominant, especially in those with more severe asthma. Mast cells are also more frequent. 3-Airway Smooth Muscle can contribute to asthma in three ways. can be hyperresponsive to stimuli hypertrophy and hyperplasia ---AWHR can produce chemokines and cytokines that promote inflammation.

27. 4.Subepithelial Collagen Deposition and Matrix Deposition Thickening of the subepithelial basement membrane Exaggerated responses to increased circumferential tension exerted by the smooth muscle. narrow the airway lumen and decrease its ability to relax and thus can contribute to chronic airway obstruction.

28. 5-Airway Epithelium The damaged epithelium forms a trophic unit which elaborates multiple growth factors as well as multiple cytokines and mediators that promote asthmatic airway inflammation------------------ Airway remodeling 6-Vascular Proliferation Secondary to elaboration of angiogenic factors in the context of airway inflammation. Inflammatory mediators can result in leakage from postcapillary venules , which can contribute to the acute and chronic edema of the airways.

29. 7- Epithelial Goblet Cell Metaplasia and Mucus Hypersecretion Chronic inflammation can result in the appearance and proliferation of mucus cells. Increased mucus production can reduce the effective airway luminal area. Mucus plugs can obstruct medium-size airways and can extend into the small airways. 8- Neuronal Proliferation Neurotrophins , which can lead to neuronal proliferation, are elaborated by smooth-muscle cells, epithelial cells , and inflammatory cells. Neuronal inputs can regulate smooth-muscle tone and mucus production, which may mediate acute bronchospasm and potentially chronically increased airway tone.

30. 9- Airway Edema Submucosal edema can be present as an acute response in asthma and as a chronic contributor to airway wall thickening.

31. AIRWAY INFLAMMATION Most asthma is accompanied by airway inflammation . In the past, asthma had been divided into Atopic asthma Relating to allergen sensitivity and exposure, with production of IgE, and occurring more commonly in children. Non-atopic (or intrinsic) asthma : occurring in individuals with later onset asthma, with or without allergies, but frequently with eosinophilia.

32. Current nosology favors consideration of whether asthma is associated with type 2 or non–type 2 inflammation.

33. Allergic Sensitization and Allergen Exposure The development of allergic sensitization involves an interplay between heritable susceptibility and allergen exposure. Allergen exposure during vulnerable developmental periods is believed to increase the risk of development of allergic sensitization. Is increased in industrialized nations. Varied microbiome exposure may influence the development of atopy with decreased risk for atopy in those in rural environments .

34. Tobacco Maternal smoking and secondhand smoke exposure are associated with increased childhood asthma. Childhood secondhand smoke exposure increased asthma risk twofold. Active smoking is estimated to increase the incidence of asthma by up to fourfold in adolescents and young adults.

35. Air Pollution Early life exposure to pollution increases the risk of development of asthma. Most risk lies with carbon monoxide and nitric dioxide , with marginal effects of sulfur dioxide . Indoor air pollution from open fires and use of gas stoves. Pollutants are thought to cause oxidative injury to the airways, producing airway inflammation and leading to remodeling and increased risk of airway sensitization.

36. Infections Incidence and frequency of human rhinovirus and respiratory syncytial virus ( RSV ) infections in children are associated with development of asthma. Evidence of prior Mycoplasma pneumoniae infection has been associated with the development of asthma in Taiwanese adults .

37. Occupational Exposures Occupational asthma is estimated to account for 10–25% of adult-onset asthma. The occupations associated with the most cases in European Community Health Surveys were nursing and cleaning . Two types of exposures are recognized: (1)an immunologic stimulus ( 2) an irritative stimulus. A combination of genetic predisposition (including atopy ), timing, intensity of exposure, and co-exposure (e.g., smoking) influences whether an individual will develop occupational asthma.

38. Diet Vitamin D insufficiency may increase asthma risk in the progeny and supplementation may decrease Maternal supplementation with vitamins C and E and zinc may decrease asthma in children. Maternal polyunsaturated fatty acid supplementation may decrease childhood asthma risk. Increased maternal sugar intake may increase childhood asthma risk. Obesity Adipokines and IL-6 have been thought to play a pathobiologic role.

39. Medications Use of H2 blockers and proton pump inhibitors in pregnancy has been associated with an increased risk of asthma in children Prenatal and Perinatal Risk Factors Preeclampsia and prematurity have been associated with increased risk of asthma in the progeny . Babies born by cesarean section are at higher risk for asthma. Those with neonatal jaundice are also at increased risk. Breast-feeding reduced early wheezing but has a less clear effect on later incidence of asthma .

40. Differential diagnosis of diseases with overlapping symptoms that can present with obstructive pulmonary function tests Heart failure Chronic obstructive pulmonary disease (COPD) α1 antitrypsin deficiency Airway obstruction from mass or foreign body Inducible laryngeal dysfunction (vocal cord dysfunction) Bronchiolitis obliterans Bronchiectasis Tracheobronchomalacia

41. Comorbidities that can make asthma difficult to control: Chronic rhinosinusitis +/– nasal polyposis Obesity Gastroesophageal reflux disease Inducible laryngeal dysfunction (vocal cord dysfunction) COPD Anxiety/depression Obstructive sleep apnea

42. Diagnosis and evaluation of asthma A presumptive diagnosis of asthma can usually be made based on a compatible history of recurrent wheezing , shortness of breath , chest tightness , or cough related to common bronchoconstrictior precipitants when appropriate components of the differential diagnosis have been considered and/or eliminated. Harrisons 21 st ed

43. Symptoms or features that support the diagnosis of asthma (Wheeze , shortness of breath , chest tightness and/or cough). Occur variably over time and vary in intensity Are often worse at night or on waking Are often triggered by exercise, laughter, allergens, cold air. Often appear or worsen with viral infections GINA 2024

44. The following features decrease the probability that respiratory symptoms are due to asthma: Chronic production of sputum Shortness of breath associated with dizziness, light-headedness or peripheral tingling ( paresthesia ) Chest pain Exercise-induced dyspnea with noisy inspiration . GINA 2024

45. GINA_2024 Update Global Strategy for Asthma Management and Prevention

46. Pulmonary Function Tests A reduction in expiratory airflow during forced expiratory maneuvers . The peak expiratory flow rate ( PEFR ), forced expiratory volume in 1 s ( FEV1 ), and the FEV1/forced vital capacity (FVC) ratio are reduced below the lower limit of normal. These findings may not be present during acute attacks or on therapy Reversibility is defined as a ≥ 12% increase in the FEV1 and an absolute increase of ≥200 mL at least 15 min after administration of a β2-agonist or after several weeks of corticosteroid therapy.

47. Diurnal peak flow variability of >20% has also been proposed as an indicator of reversible airways disease, but it is less reliable due to difficulties with quality control and variability of home assessments. Lung volumes and diffusing capacity should be normal in uncomplicated asthma.

48. Adjunctive assessment tools Eosinophil Counts A large proportion of asthma patients not treated with oral or high-dose ICSs will have eosinophil counts ≥ 300 cells/ μL . Eosinophil counts correlate with severity of disease in population studies. Their presence in patients with severe asthma indicates a likelihood that the patient would respond to medications targeted at type 2 inflammation. Extremely elevated levels should prompt consideration of eosinophilic granulomatosis with polyangiitis or primary eosinophilic disorders.

49. IgE Total serum IgE levels are useful in considering whether patients with severe asthma would be eligible for anti-IgE therapy. Levels >1000 IU/mL should prompt consideration of ABPA. Exhaled Nitric Oxide Fraction of exhaled nitric oxide ( FeNO ) in exhaled breath is an approximate indicator of eosinophilic inflammation in the airways .

50. Additional evaluation in severe/poorly responsive asthma Chest Radiography Chest CT can be useful to assess for the presence of bronchiectasis and other structural abnormalities that could produce airway obstruction. Sputum Induced sputum may be used in more specialized centers to help characterize type 2 and non–type 2 inflammation by detection of eosinophils and neutrophils, respectively.

51. TREATMENT- ASTHMA Goals of Asthma Therapy Reduction in symptom frequency to ≤2 times/week Reduction of nighttime awakenings to ≤2 times/month Reduction of reliever use to ≤2 times a week (except before exercise) No more than 1 exacerbation/year Optimization of lung function Maintenance of normal daily activities Satisfaction with asthma care with minimal or no side effects of treatment

52. A comprehensive treatment approach involves: Avoiding and reducing asthma triggers Vaccination The adjunctive use of medications(if necessary )

53. Asthma pharmacotherapy Asthma medications are primarily divided into Relievers : those that relax smooth muscle and produce a fairly rapid relief of acute symptoms. Controllers : those that target inflammation or mediator production . Reduce asthma exacerbations Improve long-term control, Decreasing the need for intermittent use of bronchodilator therapies.

54. Bronchodilators β 2-Agonists Anticholinergics Theophylline Controller (Anti-Inflammatory/ Antimediator ) Therapies Corticosteroids Leukotriene Modifiers CysLT1 Antagonists 5-Lipoxygenase Inhibition Cromolyn Sodium Anti- IgE IL-5–Active Drugs Anti–IL-4/13

55. β2- Agonists Available in inhaled or oral form Activate β2-receptors present on airway smooth muscle which results in relaxation of smooth muscle . primarily used in inhaled forms to provide relief of bronchospasm or to reduce the degree of bronchospasm anticipated in response to exercise or other provocative stimuli. Regular use has been associated with tachyphylaxis of the bronchoprotective effect and possible increased airway reactivity. Frequent short-acting β-2 agonist use has been associated with increased asthma mortality.

56. Short-Acting β2- Agonists Albuterol (also known as salbutamol) is the most commonly used agent. Bronchodilation begins within 3–5 min of inhalation, and effects generally last 4–6 h . Long-Acting β2- Agonists Salmeterol and formoterol are the two available LABAs. They have an ~12-h duration of action. Formoterol has a quick onset comparable to the short-acting β2-agonists. Salmeterol has a slower onset of action. Their use in asthma is generally restricted to use in combination with an ICS.

57. Ultra-Long-Acting β2- Agonists These agents ( indacaterol , olodaterol,and vilanterol ) have a 24-h effect. They are only used in combination with ICSs in the treatment of asthma.

58. Anticholinergic Anticholinergic medications can produce smooth-muscle relaxation by antagonizing Cholinergic nerve–induced smooth-muscle constriction. They are divided into Long-acting muscarinic antagonists (LAMAs). Short-acting muscarinic antagonists(SABAs). They appear to be somewhat less effective than β2-agonists and have a slower onset of action as well .

59. Controller ( AntiInflammatory / Antimediator ) Therapies Corticosteroids Are particularly effective in reducing type 2 inflammation and airway hyperresponsiveness . ICS and ICS/LABA ICSs are the cornerstone of asthma therapy . Their use is associated with decreased asthma mortality. They are generally used regularly twice a day as first-line therapy for all forms of persistent asthma. Doses are increased, and they are combined with LABAs to control asthma of increasing severity. European guidelines now recommend their intermittent use even in intermittent asthma .

60. Oral Corticosteroids Chronic oral corticosteroids (OCSs) at the lowest doses are used in patients who cannot achieve acceptable asthma control without them. Alternate-day dosing may be preferred, and pneumocystis pneumonia prophylaxis should be administered for those maintained on a daily prednisone dose of ≥20 mg. OCSs are also used to treat asthma exacerbations , frequently at a dose of 40–60 mg/d of prednisone or equivalent for 1–2 weeks.

61. Intravenous corticosteroids Are frequently used in hospitalized patients. Patients are rapidly transitioned to OCS once their condition has stabilized. Intramuscular Corticosteroids In high-risk, poorly adherent patients, intramuscular triamcinolone acetonide has been used to achieve asthma control and reduce exacerbations.

62. Leukotriene Modifiers Are agents that inhibit Production of leukotrienes ( zileuton , an inhibitor of 5-lipoxygenase) or Action of leukotrienes at the CysLT1 receptor ( montelukast and zafirlukast ) Are moderately effective in asthma. They can improve airway function and reduce exacerbations but not to the same degree as bronchodilators or ICS, respectively.

63. Leukotriene modifiers continued…. They are also effective in reducing symptoms of allergic rhinitis (used in patients with concomitant allergic rhinitis) Are effective in preventing exercise-induced bronchoconstriction without the tachyphylactic effects. Are particularly effective in aspirin-exacerbated respiratory disease, They have also shown modest effect as add-on therapy in patients poorly controlled on high-dose ICS/LABA.

64. Approach to the patient-asthma HARRISONS 21 st ed

65. The asthma management cycle for personalized asthma care GINA 2024

66. Patients at Greater Risk for Asthma Mortality History of intensive care unit admission for asthma History of intubation for asthma Illicit drug use Depression New diagnosis ≥ 2 emergency unit visits in past 6 months Severe psychosocial problems Lower socioeconomic status On daily prednisone prior to admission

67. Chronic Obstructive Pulmonary Disease (COPD)

68. Definition Chronic Obstructive Pulmonary Disease (COPD) is a HETEROGENEOUS lung condition characterized by CHRONIC RESPIRATORY SYMPTOMS ( dyspnea, cough, sputum production and/or exacerbations) due to abnormalities of the airways (bronchitis, bronchiolitis) and/or alveoli (emphysema) that cause PERSISTENT, OFTEN PROGRESSIVE, AIRFLOW OBSTRUCTION . GOLD 2025

69. Chronic obstructive pulmonary disease (COPD) is defined as a disease state characterized by persistent respiratory symptoms and airflow obstruction. COPD includes 1.Emphysema : an anatomically defined condition characterized by destruction of the lung alveoli with air space enlargement; 2. Chronic bronchitis : a clinically defined condition with chronic cough and phlegm ; 3. Small airway disease : a condition in which small bronchioles are narrowed and reduced in number.

70. COPD results from gene(G )- environment(E) interactions occurring over the lifetime(T ) of the individual ( GETomics ) that can damage the lungs and/or alter their normal development/aging processes . The main environmental exposures leading to COPD are tobacco smoking and the inhalation of toxic particles and gases from household and outdoor air pollution. But other environmental and host factors (including abnormal lung development and accelerated lung aging) can also contribute . The most relevant genetic risk factor for COPD identified to date are mutations in the SERPINA1 gene , leading to α1-antitrypsin deficiency.

71. COPD is the fourth leading cause of death and affects >10 million persons in the United States. COPD is also a disease of increasing public health importance around the world. Globally , there are an estimated 250 million individuals with COPD.

72. Pathogenesis of COPD Airflow obstruction, the physiologic marker of COPD, can result from airway disease and/or emphysema. Small airways may become narrowed by cells (hyperplasia and accumulation), mucus, and fibrosis. Extensive small airway destruction has been demonstrated to be a hallmark of COPD .

73. The current dominant paradigm for the pathogenesis of emphysema

74. Pathophysiology Persistent reduction in forced expiratory flow rates is the classic definition of COPD. Hyperinflation with increases in the residual volume(RV) and the residual volume/total lung capacity ratio(RV/TLC), Nonuniform distribution of ventilation, Ventilation-perfusion mismatching.

75. Pathology---COPD LARGE AIRWAYS Cigarette smoking often results in mucus gland enlargement and goblet cell hyperplasia . Bronchi also undergo squamous metaplasia, predisposing to carcinogenesis and disrupting mucociliary clearance Smooth-muscle hypertrophy and bronchial hyperreactivity leading to airflow obstruction. Neutrophil influx has been associated with purulent sputum during respiratory tract infections .

76. SMALL AIRWAYS The major site of increased resistance in most individuals with COPD is in airways ≤2 mm diameter. Characteristic cellular changes include goblet cell metaplasia , with these mucus-secreting cells replacing surfactant-secreting Club cells . Smooth-muscle hypertrophy may also be present. Luminal narrowing can occur by fibrosis, excess mucus, edema, and cellular infiltration. Reduced surfactant may increase surface tension at the air-tissue interface , predisposing to airway narrowing or collapse.

77. LUNG PARENCHYMA Emphysema is characterized by destruction of gas-exchanging air spaces, i.e ., the respiratory bronchioles, alveolar ducts, and alveoli. Large numbers of macrophages accumulate in respiratory bronchioles of essentially all smokers. Neutrophils , B lymphocytes, and T lymphocytes, particularly CD8 + cells, are also increased in the alveolar space of smokers. Alveolar walls become perforated and later obliterated with coalescence of the delicate alveolar structure into large emphysematous air spaces .

78. Clinical presentation History The three most common symptoms in COPD are cough, sputum production, and exertional dyspnea . The development of exertional dyspnea can be insidious. Activities involving significant arm work, particularly at or above shoulder level, are particularly difficult for many patients with COPD. Conversely , activities that allow the patient to brace the arms and use accessory muscles of respiration are better tolerated.

79. Physical findings In the early stages of COPD, patients usually have an entirely normal physical examination . Current smokers may have signs of active smoking. In patients with more severe disease- a prolonged expiratory phase and may include expiratory wheezing . Signs of hyperinflation include a barrel chest and enlarged lung volumes with poor diaphragmatic excursion Use of accessory muscles of respiration, sitting in the characteristic “tripod” position to facilitate the actions of the sternocleidomastoid, scalene , and intercostal muscles. Patients may develop cyanosis , visible in the lips and nail beds.

80. Tripod positioning

81. Advanced disease may be accompanied by cachexia ……..an independent poor prognostic factor in COPD. Some patients with advanced disease have paradoxical inward movement of the rib cage with inspiration ( Hoover’s sign ) Signs of cor pulmonale . NB: Clubbing of the digits is not a sign of COPD, and its presence should alert the clinician to initiate an investigation for causes of clubbing. The development of lung cancer is the most likely explanation for newly developed clubbing.

82. Laboratory findings With worsening disease severity, lung volumes may increase, resulting in an increase in total lung capacity , functional residual capacity, and residual volume. In patients with emphysema, the diffusing capacity may be reduced, reflecting the lung parenchymal destruction characteristic of the disease. Multifactorial index (BODE), incorporating airflow o bstruction , e xercise performance, d yspnea, and b ody mass index, is a better predictor of mortality.

83. INITIAL ASSESSMENT Once the diagnosis of COPD has been confirmed by spirometry , in order to guide therapy COPD assessment must focus on determining the following five fundamental aspects : Severity of airflow obstruction Nature and magnitude of current symptoms Previous history of moderate and severe exacerbations Blood eosinophil count Presence and type of other diseases ( multimorbidity )

84. GOLD grades and severity of airflow obstruction in COPD ( based on post-bronchodilator FEV1

85. Nature and magnitude of current symptoms Because there is only a weak correlation between the severity of airflow obstruction and the symptoms experienced by the patient or the impairment of their health status, formal assessment of symptoms using validated questionnaires is required.

86. Dyspnea questionnaire: the modified Medical Research Council (mMRC) dyspnea scale

87. Multidimensional questionnaires It is now recognized that COPD impacts patients beyond dyspnea.For this reason, multidimensional questionnaires are recommended .

88. CAT - INTERPRETATION Generally, the GOLD guidelines suggest using a CAT score of 10 or above to indicate symptomatic COPD.

89. Blood eosinophil count Blood eosinophil counts predict the magnitude of the effect of ICS (added on top of regular maintenance bronchodilator treatment) in preventing future exacerbations. Blood eosinophil counts are recommended by GOLD to guide the use of ICS as part of pharmacological management. Differences in airway inflammation may explain the differential response to ICS treatment according to blood eosinophil counts .

90. Multimorbidity People with COPD often suffer other concomitant chronic diseases ( multimorbidity ). This can occur in patients with mild, moderate or severe airflow obstruction . Multimorbidity influences mortality and hospitalizations independently of the severity of airflow obstruction,and deserves specific treatment. Comorbid conditions should be looked for routinely, and treated appropriately if present, in any patient with COPD. Recommendations for the diagnosis, assessment of severity, and management of individual comorbid diseases are the same as for patients without COPD.

91. Frequent multimorbid diseases in COPD include cardiovascular disease, metabolic syndrome, osteoporosis , depression and anxiety, likely in relation to shared risk factors (e.g., aging, smoking, alcohol, diet and inactivity ).

92. Combined initial COPD assessment Based on: The level of symptoms (mMRC or CAT™), The severity of airflow obstruction (GOLD grades 1-4), The frequency of previous exacerbations. This classification was proposed to guide initial pharmacological treatment.

93. Category A – 0-1 moderate exacerbations( not leading to hospitalization and mMRC 0 or 1 or CAT <10 Category B -1 moderate exacerbations( not leading to hospitalization) and mMRC >=2 or CAT >=10 Category E - >=2 Exacerbations or 1 leading to hospital admission and mMRC 0 or 1 or CAT <10 mMRC >=2 or CAT >=10

94. The combined COPD assessment allows patients with the same FEV1 (defined by the GOLD criteria) to be differentiated based on symptomatology, for example 1. a subject with an FEV1 <30% with an mMRC of 2 and three exacerbations in the past year would be labelled GOLD grade 4, group E; 2. whereas a subject with an FEV1 <30% with an mMRC of 1 and zero exacerbations in the past year would be labelled GOLD grade 4, group A

95. TREATMENT- COPD

96. STABLE PHASE COPD The institution of therapies should be based on symptom assessment, benefits of therapy, potential risks, and costs . Three interventions demonstrated to improve survival of patients with COPD — Smoking cessation, Oxygen therapy in chronically hypoxemic patients, and Lung volume reduction surgery (LVRS ) in selected patients with emphysema.

97. Pneumonia

98. Pneumonia is “an infection of the pulmonary parenchyma”. Despite being the cause of significant morbidity and mortality, it is often misdiagnosed, mistreated , and underestimated . Pneumonia historically was typically classified as: Community-acquired (CAP), Hospital-acquired (HAP ), or Ventilator-associated (VAP).

99. Rather than relying on a predefined subset or category of pneumonia cases , it is likely to be of greater value to assess each case individually on the basis of risk factors for infection with an MDR organism. At least two , if not three, risk factors are required before the probability of drug-resistant pathogens is sufficient to influence initial empirical broadspectrum antibiotic therapy .

100. Pathophysiology Pneumonia results from the proliferation of microbial pathogens at the alveolar level and the host’s response to those pathogens . Microorganisms gain access to the lower respiratory tract in several ways. Aspiration from the oropharynx Hematogenous spread (e.g., from tricuspid endocarditis) Contiguous extension from an infected pleural or mediastinal space.

101. Factors critically important in host defense The hairs and turbinates of the nares, The branching architecture of the tracheobronchial tree. Mucociliary clearance and local antibacterial factors, The gag and cough reflexes Normal flora adhering to mucosal cells of the oropharynx.

102. The host inflammatory response , rather than proliferation of microorganisms, triggers the clinical syndrome of pneumonia.

103. Decreased compliance due to capillary leak, hypoxemia, increased respiratory drive, increased secretions , and occasionally infection-related bronchospasm all lead to dyspnea . If severe enough, the changes in lung mechanics secondary to reductions in lung volume and compliance and the intrapulmonary shunting of blood may cause respiratory failure and death .

104. Pathology Classic pneumonia evolves through a series of pathologic changes . Edema phase, Red hepatization phase Gray hepatization , Resolution phase This pattern has been described best for lobar pneumococcal pneumonia and may not apply to pneumonia of all etiologies, especially viral or Pneumocystis pneumonia

105. COMMUNITY-ACQUIRED PNEUMONIA ETIOLOGY The extensive list of “ potential etiologic agents” in CAP includes bacteria,fungi , viruses, and protozoa. Most cases of CAP , however, are caused by relatively few pathogens .

106. Although Streptococcus pneumoniae is most common, other organisms must also be considered “in light of the patient’s risk factors and severity of illness”.

107. Typica l pathogens S. pneumoniae , Haemophilus influenzae , S . aureus , Gram-negative bacilli such as Klebsiella pneumoniae and Pseudomonas aeruginosa . Atypical pathogens Mycoplasma pneumoniae , Chlamydia pneumoniae , Legionella species, Respiratory viruses NB : Cannot be cultured on standard media or seen on Gram’s stain. Intrinsically resistant to all β-lactam agents and must be treated with a macrolide, a fluoroquinolone , or a tetracycline.

108. “Unfortunately , despite a careful history and physical examination as well as routine radiographic studies , the causative pathogen in a case of CAP is difficult to predict with any degree of certainty ; in more than one-half of cases, a specific etiology is never determined. Nevertheless, epidemiologic and risk factors may suggest the involvement of certain Pathogens ”

109. Epidemiologic factors suggesting possible causes of community-acquired pneumonia

110. Clinical manifestations CAP can vary “from indolent to fulminant in presentation” “from mild to fatal in severity”. Manifestations of progression and severity include both constitutional findings and those limited to the lung and associated structures.

111. Hitory The patient is frequently febrile with tachycardia or may have a history of chills and/or sweats. Cough may be either nonproductive or productive of mucoid , purulent, or blood-tinged sputum. Depending on severity, the patient may be able to speak in full sentences or may be very short of breath. If the pleura is involved, the patient may experience pleuritic chest pain. May have gastrointestinal symptoms such as nausea, vomiting, and/or diarrhea. Other symptoms may include fatigue, headache, myalgias , and arthralgias .

112. Physical findings Vary with the degree of pulmonary consolidation and the presence or absence of a significant pleural effusion . An increased respiratory rate and use of accessory muscles of respiration are common. Reveal increased or decreased tactile fremitus, Percussion note can vary from dull to flat, Crackles , bronchial breath sounds, and possibly a pleural friction rub may be heard on auscultation. The clinical presentation may not be so obvious in the elderly, who may initially display new-onset or worsening confusion and few other manifestations. Severely ill patients may have septic shock and evidence of organ failure.

113. The risk of cardiac complications secondary to enhanced inflammation and procoagulant activity is increased . These complications include myocardial infarction, congestive heart failure, and arrhythmias,particularly in the elderly. In pneumococcal CAP, the increased risk of acute coronary events may be partially driven by pneumolysis , which increases platelet activation. Up to 90% of acute coronary syndromes occur in the first week after onset of CAP, and the risk of new-onset congestive heart failure in elderly hospitalized CAP patients can extend up to 1 year.

114. DIAGNOSIS When confronted with possible CAP, the physician must ask two questions : Is this pneumonia? Typically answered by clinical and radiographic methods If so, what is the likely etiology ? Requires the aid of laboratory techniques.

115. The differential diagnosis includes both infectious and noninfectious entities Acute bronchitis, Acute exacerbations of chronic bronchitis, heart failure, pulmonary embolism, hypersensitivity pneumonitis , radiation pneumonitis

116. Clinical diagnosis Unfortunately , the sensitivity and specificity of the findings on physical examination are less than ideal, averaging 58% and 67 %, respectively . chest radiography is often necessary To differentiate CAP from other conditions. Findings may include risk factors for increased severity (e.g., cavitation or multilobar involvement). Results suggest an etiologic diagnosis .( pneumatoceles suggest infection with S. aureus , and an upper-lobe cavitating lesion suggests tuberculosis. CT may be of value in a patient with suspected postobstructive pneumonia caused by a tumor or foreign body or suspected cavitary disease.

117. pneumatocele cavity

118. bronchopneumonia Bilateral interstitial infiltrates

119. Etiologic Diagnosis The etiology of pneumonia usually cannot be determined solely on the basis of clinical presentation. Except for CAP patients admitted to the ICU, no data exist to show that treatment directed at a specific pathogen is statistically superior to empirical therapy. The benefit of establishing a microbial etiology can therefore be questioned , particularly in light of the cost of diagnostic testing.

120. Gram’s stain and culture of sputum The main purpose of the sputum Gram’s stain is to ensure that a sample is suitable for culture . To be adequate for culture, a sputum sample must have >25 neutrophils and <10 squamous epithelial cells per low-power field. The sensitivity and specificity of the sputum Gram’s stain and culture are highly variable. Even in cases of proven bacteremic pneumococcal pneumonia , the yield of positive cultures from sputum samples is ≤50%.

121. Blood cultures The yield even when samples are collected before antibiotic therapy, is disappointingly low . Only 5–14 % of cultures of blood from patients hospitalized with CAP are positive , and the most frequently isolated pathogen is S. pneumoniae . Certain highrisk patients —including those with neutropenia secondary to pneumonia, asplenia , complement deficiencies, chronic liver disease, or severe CAP —should have blood cultured.

122. Urinary antigen tests Two commercially available tests detect pneumococcal and Legionella antigen in urine. The sensitivity and specificity of the Legionella urine antigen test are as high as 70% and 99%, respectively. The pneumococcal urine antigen test is also quite sensitive and specific ( 70% and >90 %, respectively ).

123. Polymerase chain reaction pcr tests Has become the standard for diagnosis of respiratory viral infection. PCR can detect the nucleic acid of Legionella species, M. pneumoniae , C. pneumoniae,and mycobacteria.

124. Treatment- CAP SITE OF CARE Tools that objectively assess the risk of adverse outcomes, including severe illness and death , can minimize unnecessary hospital admissions. Although a number of prediction rules exist, the two most frequently used are : The Pneumonia Severity Index ( PSI ), a prognostic model used to identify patients at low risk of dying, The CURB-65 criteria, a severity-of-illness score.

125. PSI

126. The IDSA/ATS criteria for severe community-acquired pneumonia (CAP) Are composed of both major and minor criteria. Although the major criteria indicate clear need for ICU-level care, the minor criteria for defining severe CAP have been validated for the use of differentiating between patients requiring ward-level versus ICU-level care .

127. Initial antibiotic management Since the etiology of CAP is rarely known at the outset of treatment, initial therapy is usually empirical, designed to cover the most likely pathogens.

128. Adjunctive measures Adequate hydration, oxygen therapy for hypoxemia , Vasopressors, and Assisted ventilation when necessary

129. Failure to improve Patients slow to respond to therapy should be reevaluated at about day 3 (sooner if their condition is worsening rather than simply not improving),. Several possible scenarios should be considered. noninfectious conditions mimic pneumonia( see differential diagnosis above). Correct diagnosis, appropriate empiric management but Resistant pathogen Sequestered focus The wrong drug or the correct drug at the wrong dose or frequency of administration correct diagnosis but an unsuspected pathogen (e.g., CA-MRSA, M. tuberculosis, or a fungus ). Nosocomial superinfections ( either pulmonary and extrapulmonary )

130. Complications of severe CAP include Respiratory failure, Shock and multiorgan failure, Coagulopathy , and Exacerbation of comorbidillnesses . Three particularly noteworthy conditions are metastatic infection , lung abscess, and complicated pleural effusion ..

131. Follow-up Fever and leukocytosis usually resolve within 2–4 days in otherwise healthy patients with CAP, but physical findings may persist longer. Chest radiographic abnormalities are slowest to resolve (4–12 weeks ), with the speed of clearance depending on the patient’s age and underlying lung disease. For a hospitalized patient, a follow-up radiograph ~4–6 weeks later is recommended. If relapse or recurrence is documented, particularly in the same lung segment, the possibility of an underlying neoplasm must be considered.

132. The prognosis of CAP depends on : The patient’s age and comorbidities, Young patients without comorbidity do well and usually recover fully after ~2 weeks. Older patients and those with comorbid conditions can take several weeks longer to recover fully. Site of treatment (inpatient or outpatient). The overall mortality rate for the outpatient group is <5%. For patients requiring hospitalization, the overall mortality rate ranges from 2 to 40 %.

133. Interstitial lung diseases

134. Interstitial lung disease is a clinical term for a heterogenous group of acute and chronic lower respiratory tract disorders with many potential causes. Clinical and physiologic features commonly include Cough , exertional dyspnea. Absence of pulmonary infection or neoplasm , Abnormal pulmonary physiology, including a restrictive pattern on pulmonary function testing. Coexistent airflow obstruction, Decreased diffusing capacity ( Dlco ), Increased alveolar-arterial oxygen difference (Pao2-Pao2 ) at rest or during exertion.

135. The term interstitial is a misnomer because the pathologic processes are not restricted to the interstitium but : All of the cellular and soluble constituents that make up the gas exchange units. The bronchiolar lumen, terminal bronchioles, and pulmonary parenchyma beyond the gas exchange units The pleura and lymphatics and sometimes the lymph nodes . May be involved in the pathogenesis and manifestations of interstitial lung disease.

136. The overall incidence is higher in men (31.5 per 100,000 per year) than in women (26.1 per 100,000 per year ). The prevalence of undiagnosed or early interstitial lung disease is estimated to be 10 times that of clinically recognized disease Among the interstitial lung diseases, the two most common are idiopathic pulmonary fibrosis and connective tissue–associated disease.

137. How do patients come to medical attention? Reports of progressive exertional dyspnea or a persistent dry cough. Nonrespiratory symptomatology related to multisystem disorders. Incidentally based on the results of abnormal pulmonary function tests and/or chest imaging.

138. Owing to a variety of clinical presentations, as well as overlapping imaging and histopathologic findings, ILDs can be difficult to diagnose. “ ILD diagnosis is that the combined weight of clinical data, laboratory studies, pulmonary function testing, imaging findings, and histopathology (if obtained) are jointly required to make a confident diagnosis .” No single piece of data confers a diagnosis alone.

139. ILDs are classified as Of known and Of unknown causes

140. Diagnostic approach History Age The age of onset of clinical symptoms has a strong influence on the pretest probability of a p articular ILD. IPF occurs most commonly in patients aged >60 and is quite rare among patients aged <50. Sarcoidosis , CTD-associated ILD, LAM and pulmonary Langerhans cell histiocytosis (PLCH), tend to present between the ages of 20 and 40.

141. Sex Less influential than age . LAM is a disorder that is frequently diagnosed in young women. Many CTD-associated ILDs are more common among women. RA-associated ILD, which is more common among men. IPF and occupational/exposure-related ILDs are more common among men.

142. Duration of Symptoms ILDs most commonly have a chronic indolent presentation (months to years ). Acute presentations (days to weeks) of ILD are unusual. ILDs that can present acutely include Eosinophilic pneumonia, Acute interstitial pneumonia (AIP ), Hypersensitivity pneumonitis(HP), Granulomatosis with polyangiitis ( GPA) acute exacerbation of IPF Subacute presentations (weeks to months ) can occur in most of the ILDs but typically in: Sarcoidosis , CTD- associatedILD , Drug-induced ILD, COP

143. Respiratory Symptoms Dyspnea : Progressive dyspnea, most frequently noted with exertion, is the most common complaint. Some patients, even those with more extensive disease on chest CT imaging, may not report dyspnea. Fatigue is common to all of the ILDs . Dry cough : is also common and can be the most prominent symptom in patients with IPF, sarcoidosis and HP. Cough with hemoptysis : is rare and could suggest an ILD associated with Diffuse alveolar hemorrhage(DAH) (e.g., Goodpasture’s syndrome), GPA, or LAM. A secondary pulmonary infection that can be seen in patients with traction bronchiectasis. Chest pain : is rare in most of the ILDs , with the exception of sarcoidosis .

144. Past Medical History Personal history of a CTD or a history of symptoms commonly associated with a CTD (the most pertinent history) A history of malignancy is important (some malignancies can be associated with dermatomyositis -associated COP and sarcoid -like reactions. A history of asthma and allergic rhinitis might suggest a diagnosis of eosinophilic GPA.

145. Medications Many medications have been associated with ILD, Specific medications in many classes are also known to cause ILD, including Antibiotics (e.g., nitrofurantoin ), Antiarrhythmics (e.g., amiodarone ), Antineoplastic agents (e.g., bleomycin ). Many medications commonly used to treat inflammatory and granulomatous lung disease are also associated with ILD development (e.g., methotrexate, azathioprine, rituximab , and the tumor necrosis factor α–blocking agents).

146. Family History The presence of a close relative with an IIP is among the strongest risk factors for IPF . The most well-replicated genetic factors for pulmonary fibrosis (a mucin gene (MUC5B )

147. Social History A history of smoking is nearly always present in some forms of ILD (e.g., respiratory bronchiolitis and DIP—AKA smoking-related ILDs). A history of smoking is also noted in approximately three-quarters of IPF patients. Occupational and environmental exposure {(e.g ., asbestos exposure ) or HP (pigeon breeder’s lung )}

148. PHYSICAL EXAMINATION End-inspiratory fine crackles, or rales , noted at the lung bases are found in most patients with IPF and may be one of the earliest signs of the disease. However , rales are nonspecific and can be found in many forms of ILD and other disorders. Wheezing is uncommon in most forms of ILD but can be present in some disorders, such as sarcoidosis , HP , and eosinophilic GPA. Signs of advanced disease include cyanosis, digital clubbing, and cor pulmonale .

149. LABORATORY STUDIES Particularly helpful in the workup for an underlying CTD -associated ILD. e.g., A positive anti-cyclic citrullinated peptide [anti-CCP] antibody for RA ).

150. PULMONARY FUNCTION TESTS Most forms of ILD will eventually result in a restrictive deficit in pulmonary function testing. i.e A reduced total lung capacity (TLC) and sFEV1 ) and forced vital capacity (FVC). A reduction in the diffusing capacity of the lung for carbon monoxide ( DlCO ) is also common and may precede a reduction in lung volumes; PFTs characterize the extent of disease. A decline in repeated measures of pulmonary function (e.g., FVC) has been correlated with an elevated mortality rate.

151. CHEST IMAGING STUDIES Findings on CXR Can be the first clinical indication that an ILD might be present. Eg . enlarged hilar lymph nodes and a pattern of central nodular opacities in the mid to upper lung zones can suggest sarcoidosis . A basilar reticular pattern, with small cystic spaces, in the absence of clinical evidence for heart failure, might suggest IPF. With a few exceptions, CXRs alone rarely lead to a specific diagnosis.

152. High-resolution CT (HRCT) Can be diagnostic for some ILDs (e.g., IPF) in the right clinical context and may preclude the need for, and spare the patient the risk of, a lung biopsy. HRCT also helps to Define the extent of the ILD, Determine the presence of more concerning features suggestive of advanced disease (e.g., honeycombing), Provide information on coexisting diseases (e.g., emphysema and lung cancer), Provide the most useful locations for obtaining lung biopsy specimens

153. Principles of management-ILD ONGOING MONITORING GENERAL CARE MEASURES SPECIFIC TREATMENT

154. Ongoing monitoring Pulmonary symptoms and signs Non pulmonary symptoms Recent ILD exacerbation or other hospitalization Drug side effects and toxicities Pulmonary function testing Surveillance and monitoring of autoantibodies Surveillance for pulmonary hypertension ( PH) Serial HRCT imaging is recommended at regular intervals ( eg , every 6 to 12 months) for individuals with progressive or active ILD. Lung cancer screening evaluations

155. General Care Measures Comorbidity identification and management Nutritional support Tobacco cessation Supplemental oxygen Pulmonary rehabilitation Prevention of pulmonary infections and acute exacerbations of ILD -Vaccination Removal of the exposure in Exposure-associated ILDs Antifibrotics ( Nintedanib , Pirfenidone )

156. Pulmonary hypertension

157. Pulmonary hypertension Introduction It is a pathological condition of the pulmonary vasculature present in several disease states( i.e heterogeneous) that presents with elevated mean pulmonary artery pressure (PAP) as measured by right heart catheterization at rest . Involves pathogenic remodeling of the pulmonary vasculature, which increases pulmonary artery pressure and vascular resistance. The most common causes of PH are left heart or primary lung disease; If left untreated, PH carries a high mortality rate, largely owing to decompensated right heart failure.

158. Classification of Pulmonary Hypertension Group 1-Pulmonary arterial hypertension (PAH ) Disorders associated with PAH : Congenital heart disorders Connective tissue disorders HIV infection Portal hypertension Schistosomiasis Drug- and toxin-induced PAH Heritable PAH Idiopathic PAH

159. Group 2 - Pulmonary hypertension with left-heart disease Congenital or acquired left heart inflow or outflow tract obstruction and congenital cardiomyopathies Left heart diastolic dysfunction, including left heart failure with preserved ejection fraction Left heart systolic dysfunction Valvular heart disorders

160. Group 3-Pulmonary hypertension associated with lung disorders, hypercarbic,hypoxemic , or both Alveolar hypoventilation disorders Chronic exposure to high altitude Chronic obstructive pulmonary disease (COPD ) Developmental abnormalities Interstitial lung disease Lymphangioleiomyomatosis Sleep-disordered breathing(OSA) Other pulmonary disorders with a mixed restrictive and obstructive pattern

161. Group 4-Pulmonary hypertension due to pulmonary artery obstructions Nonthrombotic pulmonary embolism ( eg , due to tumors, parasites, or foreign materials ) Thromboembolic obstruction of distal or proximal pulmonary arteries

162. Group 5-Miscellaneous (unclear or multifactorial mechanisms Hematologic disorders (Chronic hemolytic anemia, Myeloproliferative disorders,Sickle cell disease Systemic disorders:Pulmonary Langerhans cell histiocytosis , Sarcoidosis Metabolic disorders: Gaucher disease, Glycogen storage disease Thyroid disorders Other disorders : Chronic kidney disease Fibrosing mediastinitis Segmental pulmonary hypertension Tumor, causing obstruction

163. Pathophysiology of Pulmonary Hypertension Pathophysiologic mechanisms that cause pulmonary hypertension include Increased pulmonary vascular resistance Increased pulmonary venous pressure Increased pulmonary venous flow due to congenital heart diseases

164. A)Increased pulmonary vascular resistance Is caused by obliteration of the pulmonary vascular bed and/or by pathologic vasoconstriction . Characterized by endothelial and smooth muscle proliferation, hypertrophy, and chronic inflammation , resulting in vascular wall remodeling . The increased pulmonary vascular pressure that results from vascular obstruction further injures the endothelium. Injury activates coagulation at the intimal surface , which may worsen the hypertension.

165. B)Increased pulmonary venous pressure Caused by disorders that affect the left side of the heart and raise left chamber pressures, which ultimately lead to elevated pressure in the pulmonary veins. Persistently high pressures may eventually lead to irreversible thickening of the walls of the alveolar-capillary membrane . The most common setting for pulmonary venous hypertension is in left heart failure with preserved ejection fraction ( HFpEF ), typically in older women who have hypertension and metabolic syndrome . NB:pulmonary hypertension eventually leads to right ventricular hypertrophy followed by dilation and right ventricular failure.

166. C) Increased pulmonary venous blood flow due to congenital heart disease can cause pulmonary hypertension. This can occur in conditions such as atrial septal defects, ventricular septal defects, and patent ductus arteriosus .

167. Symptoms and Signs of Pulmonary Hypertension Progressive exertional dyspnea and easy fatigability occur in almost all patients. Atypical chest discomfort and exertional light-headedness or presyncope may accompany dyspnea and indicate more severe disease. These symptoms are due primarily to insufficient cardiac output caused by right heart failure. Raynaud syndrome occurs in about 10% of patients with idiopathic pulmonary arterial hypertension; the majority are women. Hoarseness due to recurrent laryngeal nerve compression by an enlarged pulmonary artery ( ie , Ortner syndrome ) also occurs rarely.

168. Ortner’s syndrome aortic aneurysms, pulmonary hypertension, left atrial enlargement, congenital cardiac disorders.

169. In advanced disease, signs of right heart failure may include Right ventricular heave, Widely split 2nd heart sound (S2), Accentuated pulmonic component (P2) of S2, A pulmonary ejection click, A right ventricular 3rd heart sound (S3), Tricuspid regurgitation murmur, and jugular vein distention, Liver congestion and peripheral edema Pulmonary auscultation is usually normal. Patients also may have manifestations of causative or associated disorders.

170. Diagnosis of Pulmonary Hypertension Exertional dyspnea-suspect Initial evaluation: Chest x-ray- enlargement of pulmonary arteries and obliteration of the retrosternal space ECG- right ventricular hypertrophy or strain. Echocardiography- Elevated estimated pulmonary artery systolic pressure (>35 mmHg) a hypertrophied or dilated right ventricle. valvular disease, left ventricular systolic and diastolic function, left atrial enlargement, and intracardiac shunt

171. right-axis deviation >120° (A), right ventricular hypertrophy (B), right atrial enlargement (C) and right ventricular strain (D).

172. Identification of underlying disorder: Spirometry , ventilation/perfusion scanning or CT angiography, high-resolution CT (HRCT) of the chest, pulmonary function testing, polysomnography , HIV testing, complete blood count, liver tests, and autoantibody testing Confirmation of the diagnosis and gauging severity : Pulmonary artery (right heart) catheterization Additional studies to determine severity: 6-minute walk distance plasma levels of N-terminal pro-brain natriuretic peptide (NT- proBNP ) or BNP

173. Treatment of Pulmonary Hypertension-principles Avoidance of activities that may exacerbate the condition ( eg , cigarette smoking, high altitude, pregnancy, use of sympathomimetics ) Idiopathic and familial pulmonary arterial hypertension: IV epoprostenol ; inhaled, oral, subcutaneous, or IV prostacyclin analogs; oral endothelin -receptor antagonists; oral phosphodiesterase 5 inhibitors, oral soluble guanylate cyclase stimulators; oral prostacyclin (IP2) receptor agonists Secondary pulmonary arterial hypertension: Treatment of the underlying disorder Lung transplantation Adjunctive therapy: Supplemental oxygen, diuretics, and/or anticoagulants

174. Prognosis for Pulmonary Hypertension Indicators of a poorer prognosis include Lack of response to vasodilators Hypoxemia Reduced overall physical functioning Low 6-minute walk distance High plasma levels of NT-pro-BNP or BNP Echocardiographic indicators of right heart systolic dysfunction Right heart catheterization showing low cardiac output, very high mean pulmonary artery pressures, and/or high right atrial pressures

175. References Harrisons principles of internal medicine uptodate