Respiratory Disorders Module 4 Slides PDF

Respiratory Disorders Ontario Primary Healthcare Nurse Practitioner Program Outline • Respiratory System (background) • Obstructive Disorders – Asthma – COPD • Lung Cancer • Respiratory Infections – Tuberculosis – RSV – Pneumonia Background RESPIRATORY SYSTEM Respiratory System Function • T...

Respiratory Disorders Ontario Primary Healthcare Nurse Practitioner Program Outline • Respiratory System (background) • Obstructive Disorders – Asthma – COPD • Lung Cancer • Respiratory Infections – Tuberculosis – RSV – Pneumonia Background RESPIRATORY SYSTEM Respiratory System Function • The primary functions of the respiratory system are: – – – – Gas exchange between atmosphere and blood Protection from inhaled pathogens and irritants Regulation of body pH Vocalization (phonation) Respiratory System Overview of structures Upper Airways • Nasal cavity • Pharynx • Larynx Lower Airways • • • • • Larynx Trachea Bronchi Bronchioles Alveoli Respiratory System Lower airways Small cross-sectional area Huge cross-sectional area Respiratory System Mucociliary apparatus Respiratory System Gas exchange membrane (alveoli) Respiratory System Circulations Bronchial arteries (from LV)* Supply conducting airways from trachea to terminal bronchioles. Pulmonary arteries (from RV) Supply the respiratory regions of the lung, otherwise known as the acinus. Acinus = terminal bronchiole, respiratory bronchioles, alveolar ducts, alveolar sacs, alveoli; all wrapped in elastic connective tissue. * not shown Elastic tissue surrounding an acinus Respiratory System Gas exchange The exchange of O2 between alveoli, blood, and tissues occurs in 4 stages: 1. Ventilation of the lungs (alveoli) 2. Diffusion of oxygen from the alveoli into the capillary blood 3. Perfusion of systemic capillaries with oxygenated blood 4. Diffusion of oxygen from systemic capillaries into the cells Delivery of CO2 from cells to the environment occurs in the reverse order. All driven by differences in partial pressures of O2 and CO2. Respiratory System Gas exchange (diffusion into circulation) Type II Respiratory System Gas exchange (diffusion into cells) Respiratory System Ventilation mechanics Works on Boyles law: pressure x volume = constant Simply put: Increased volume = Decreased Pressure Decreased volume = Increased Pressure Expansion of chest wall and downward movement of diaphragm act to increased thoracic volume (decrease intrapulmonary pressure), resulting in inspiration. Recoil of lung and chest wall, and relaxation of diaphragm act to decrease thoracic volume (increase intrapulmonary pressure), resulting in expiration. This is passive at rest. Respiratory System Ventilation-perfusion matching To ensure that gas exchange occurs in an optimal fashion, blood is preferentially sent to the portions of the lung that are well ventilated, and diverted from regions of the lung that are not. We call this ventilation/perfusion matching. Respiratory System Ventilation-perfusion mismatch Sometimes there are regions of the lung where there is an imbalance between how well it is ventilated and how well it is. perfused with blood. . This imbalance is described as an abnormal V/Q ratio. . . Normal V/Q ratio . . . High V/Q ratio High V . High Q PAO2 = 105 PACO2 = 40 . . . Low V/Q ratio High V . Low Q PAO2 = ↑ PACO2 = ↓ Not enough perfusion of a well-ventilated area • Apex of lung • Pulmonary embolism . Low V . High Q PAO2 = ↓ PACO2 = ↑ Not enough ventilation of a well perfused area • Base of lung • Asthma • Lung cancer Respiratory System How do we correct for ventilation-perfusion mismatch? It's all about the pulmonary arterioles! – Arterioles relax if PACO2 is low or PAO2 is high – Arterioles constrict if PACO2 is high or PAO2 is low • Otherwise known as hypoxic pulmonary vasoconstriction . . High V/Q ratio . . . Low V/Q ratio High V . Low Q PAO2 = high PACO2 = low Pulmonary arterioles relax . Low V . High Q PAO2 = low PACO2 = high Pulmonary arterioles constrict Respiratory System Signs & symptoms of pulmonary disease / injury • Dyspnea is the experience of breathing discomfort • Cough is a protective reflex that helps to clear lower airways – Acute (2-3 weeks), Chronic (>3weeks) • Abnormal sputum (hemoptysis) • Abnormal breathing patterns – Hyperpnea (Kussmaul respirations), laboured, tachypnea • Hyperventilation, hypoventilation • Cyanosis Respiratory System Conditions caused by pulmonary disease / injury • Hypercapnia – ↑PaCO2 in the blood – Triggers reflex to increase ventilation, vasodilation • Hypoxemia – ↓PaO2 in arterial blood – can present as cyanosis • Acute respiratory failure – hypoxemia or hypercapnia with a pH ≤ 7.25 CO2 + H2O ó H2CO3 ó HCO3- + H+ Respiratory System Obstructive vs restrictive lung disease • Obstructive – Difficulties on expiration (getting air out of lungs) – Higher amount of air remains in the lungs -> SOB – Due to damaged lungs or narrowed airways (e.g., asthma, COPD, cystic fibrosis, bronchiolitis obliterans, etc.) • Restrictive – Lungs are prevented from fully expanding – Can be intrinsic (e.g., interstitial lung disease, adverse reaction to drugs) or extrinsic (e.g., chest wall and neuromuscular disorders) Johnson JD et.al. (2014) Am Fam Physician. 89(5):359-366 http://www.ucalgary.ca/icancontrolasthma/files/icancontrolasthma/movie_1.swf Asthma OBSTRUCTIVE DISORDERS Asthma Overview • “Asthma is an inflammatory disorder of the airways characterized by paroxysmal or persistent symptoms such as dyspnea, chest tightness, wheezing, sputum production and cough, associated with variable airflow limitation and airway hyper-responsiveness to endogenous or exogenous stimuli. Inflammation and its resultant effects on airway structure and function are considered to be the main mechanisms leading to the development and maintenance of asthma” (CTS, 2021) • Major characteristics of this obstructive disorder include: – Bronchial hyperresponsiveness, airway inflammation, airway remodeling • Genetic and environmental factors contribute to pathogenesis – Most common phenotype = allergic asthma – Family history of atopy/allergies/asthma – Urban residence, recurrent viral respiratory infections, pollution, cigarette smoke & obesity Asthma Epidemiology • • • • • Prevalence of asthma is increasing Asthma is a major cause of hospitalization of children Higher prevalence in male children and adult females FNIM most affected Highest rates in ON, NS; lowest NT, YT, NU. PHAC (2018) OASIS & ICES (2018) Asthma Annual trends (Ontario) • 20-25% of asthma exacerbations in Ontario children occur in September • Adults tend to experience more exacerbations in the winter months Asthma Pathophysiology • Inhaled allergens are picked up in the airways by antigen presenting cells (e.g., dendritic cells and macrophages) – • • • • This occurs in healthy individuals too The allergen, which is a harmless foreign object, is recognized as harmful Antigen presenting cells migrate to draining lymph nodes and present the allergen to T helper cells in the context of MHC II T helper cells become activated and initiate an immune response The immune response that occurs during asthma is predominantly mediated by Th2 cells which secrete the cytokines IL-4, IL-5, IL-8 and IL-13 N Engl J Med (2001) Vol. 344, No. 5 Nature Reviews Immunology 8, 218-230 (March 2008) Asthma Pathophysiology continued • Activated Th2 cells activate B cells specific to the allergen • B cells differentiate into plasma cells and begin to synthesize/secrete IgE antibodies • IgE antibodies bind to high affinity receptors on the surface of mast cells, B cells, basophils, eosinophils, and macrophages • During subsequent exposure, the allergen is picked up by IgE bound to these cells, causing them to degranulate and/or become activated Th2 T Helper Cell Basophil Eosinophil Macrophage 1 2 N Engl J Med (2001) Vol. 344, No. 5 3 Asthma Early phase of inflammation • Early inflammation occurs immediately after allergen exposure and subsides within approximately 1 hour. • During the early inflammatory response, mast cells release histamine and leukotrienes. • Histamine – Promotes bronchoconstriction – Stimulates vasodilation and increases vascular permeability, which causes edema of the airways – Stimulates mucus secretion – Increases expression of adhesion molecules on endothelial cells • Leukotrienes – Promote bronchoconstriction – Recruit neutrophils and eosinophils to the bronchioles – Stimulate mucus secretion Asthma Early phase of inflammation continued • Bronchoconstriction, edema and mucus hypersecretion that narrow the airway lumen and obstruct airflow • Patients exhibit symptoms of wheeze, non-productive cough, dyspnea, tachycardia, tachypnea, SOB, prolonged expiration, and tightness in the chest. http://www.webmd.com/asthma/ss/slideshow-asthma-overview Asthma Early phase of inflammation continued • Airway obstruction makes it difficult to exhale • Air becomes trapped in alveoli distal to obstructed areas, which decreases ventilation to these alveoli • Body tries to compensate by decreasing perfusion of these alveoli, but perfusion ventilation mismatches still occur • Patients become hypoxic • Lung receptors are activated and promote hyperventilation • at this point arterial O2 is low but CO2 levels are normal or low • Chemoreceptors also become activated, further increasing respiratory rate (tachypnea) • In some cases, air trapping becomes more severe, and patients begin to retain CO2 (hypercapnia) • CO2 retention results in respiratory acidosis, which can be life-threatening. Asthma Late phase of inflammation • A late inflammatory response can occur within 4-8 hours of an asthma attack and persists for 24-48 hours – can be more severe than the original attack • The late phase of inflammation is characterized by the recruitment of eosinophils, basophils, neutrophils, macrophages and Th2 cells to the bronchioles • Eosinophils release proinflammatory cytokines and cytotoxic mediators that promote vascular leakage, mucus hypersecretion, bronchoconstriction and airway hyperresponsiveness – Ultimately results in a second bout of obstructed airflow Asthma Airway hyperresponsiveness • Increased ability of the airways to narrow after exposure to constrictor agents • Consists of two components: – Hypersensitivity – Hyperreactivity Chest. 2003 Mar;123(3 Suppl):411S-6S Asthma Airway remodeling • Asthma patients exhibit low grade chronic inflammation in the absence of allergens • Over time, untreated chronic inflammation or repeat exacerbations of asthma results in airway remodeling – Smooth muscle cell hypertrophy and hyperplasia – Increased extracellular matrix deposition (subepithelial fibrosis) – Goblet cell hyperplasia – Epithelial cell proliferation – Increased vascularity • Further perpetuates asthma http://www.news-medical.net/health/Asthma.aspx Asthma Clinical manifestations • No clinical symptoms between asthma attacks and pulmonary function tests are normal • History of wheezing, coughing, shortness of breath and/or tightness in chest • Symptoms worsen with exercise, cold air, viral infection, allergens, irritants, and stress • With severe attacks there may be air tapping, lung hyperinflation, recruitment of accessory muscles, severe dyspnea, and fatigue. • There is a decrease in peak expiratory flow (PEF) as assessed using spirometry Asthma Home monitoring & lung function tests Green 80-100% of personal best Yellow 50-80% of personal best – take bronchodilator, repeat measure Red Below 50% personal best – take bronchodilator, call 911 http://www.drugs.com/cg/how-to-use-a-peak-flow-meter.html http://www.abpischools.org.uk/page/modules/breathingandasthma/asthma7.cfm?age=Age%20ra nge%2014-16&subject=Physical%20education Asthma Summary • Characterized by inflammation, bronchial hyperresponsiveness, and reversible airway obstruction • Link with allergic disease (Th2, mast cells, eosinophils) • Early response – mast cell products causing bronchoconstriction > wheeze, hypoxemia, hyperventilation, respiratory alkalosis • Late response – influx of eosinophils with further bronchoconstriction > hyperinflation, hypoxemia, hypercapnia, respiratory failure • Recurrent attacks or chronic inflammation > airway remodeling (epithelium, ASM, vasculature) COPD OBSTRUCTIVE DISORDERS http://www.mamanathome.com/article-la-cigarette-et-moi-68578056.html COPD Overview • COPD is “a common, preventable, and treatable disease characterized by persistent airflow limitation that is usually progressive and is associated with an enhanced chronic inflammatory response in the airways to noxious particles or gases. Chronic inflammation causes structural changes and narrowing of the small airways in the lungs.” (GOLD, 2016) • Two overlapping phenotypes (chronic bronchitis, emphysema) • COPD often occurs later in life Main Risk Factors include: • Common symptoms include – – – – Dyspnea, SOB Chronic cough Excessive sputum production Exercise intolerance • • • • Tobacco smoking Occupational dusts and chemicals (vapours, irritants, and fumes) Indoor air pollution (biomass fuel used for cooking & heating) Outdoor air pollution COPD Epidemiology • Global statistics (WHO, 2019) – Responsible for approximately 3 million deaths annually – Third leading cause of death worldwide – Tobacco smoke accounts for 70% of COPD in high-income countries and 3040% in LMIC –> household air pollution is a major risk factor – 1.3 billion smokers world-wide (~37% of males and ~8% of females) • Canadian statistics (PHAC, CCDSS 2018 data) – In those >35 years, prevalence increased steadily across the life span – prevalence higher in males than females in the >60 years age group – Incidence and prevalence was highest in NU, YT, NS and NT – All cause mortality rate is higher in those with COPD across all age groups • COPD (1-3%) is caused by an inherited mutation in α1-antitrypsin gene – AAT protects lung tissue from proteolytic enzymes that break down elastin – Mutations in α1-antitrypsin gene promote emphysema in non-smokers COPD Pathophysiology of emphysema • Chronic inflammatory condition characterized by abnormal permanent enlargement of the gasexchange airways accompanied by destruction of alveolar walls without obvious fibrosis • Inspired irritants promote inflammation within the airway wall Inflammation is predominantly mediated by Th1 cells and is characterized by macrophage, neutrophil and lymphocyte infiltration Macrophages and neutrophils release proteolytic enzymes that destroy alveoli Decreased number of alveoli reduces surface area of lungs and impairs oxygen extraction Loss of elastin fibers reduces lung recoil (increases compliance), makes bronchioles less stable and more prone to collapse, making it more difficult to expire • • • • COPD Pathophysiology of emphysema continued Loss of elastic recoil results in early collapse of small airways. Difficulty exhaling due to decreased elastic recoil (increased compliance) of alveolus, narrowed bronchioles and air trapping. Air trapping contributes to retention of CO2 (hypercapnia) and results in respiratory acidosis. http://www.pneumrx.com/for-physicians/gps-referring-physicians/ Patients often evoke pursed lip breathing on expiration to prevent small airways collapse. COPD Pathophysiology of chronic bronchitis • Defined as hypersecretion of mucus and chronic productive cough that lasts for at least 3 months of the year for at least 2 consecutive years • Inspired irritants promote inflammation within the airway wall • Inflammation is predominantly mediated by Th1 cells (macrophage and cytotoxic T cell infiltration) and increased release of IL-1β and TNF-α • Cytokines stimulate increased mucus production through an increase in the size and number of mucous glands and goblet cells in airway epithelium • The mucus is thicker than normal • Ciliary function is impaired, further reducing mucous clearance • Goblet cell hyperplasia decreases the diameter of the lumen • Excess mucous increases airway surface tension, making airways prone to collapse COPD Pathophysiology of chronic bronchitis continued • Bacteria become embedded in airway secretions and begin to reproduce and cause infections/injury • Inflammation is exacerbated, which further increases mucous production • Airway walls become edematous, reducing airflow • Over time, inflammation causes airway remodeling • Smooth muscle cells undergo hypertrophy and airways become more narrow • Respiratory tract epithelium undergoes metaplasia and converts to squamous epithelial cells • Increased deposition of extracellular matrix proteins COPD Pathophysiology of chronic bronchitis & emphysema • Both emphysema and chronic bronchitis are characterized by expiratory flow limitation • In emphysema, this is due to a loss of elastic tissue and in chronic bronchitis this is due to mucous hypersecretion • Expiratory flow limitation increases the amount of air left in the lungs at the end of expiration through a process known as air trapping • Over time, the lungs begin to hyperinflate, which makes the respiratory muscles less effective • In addition, at higher lung volumes, greater pressure changes are required to move air into the lungs, which requires more work from the respiratory muscles • These alterations increase the work of breathing and cause dyspnea COPD Pathophysiology of chronic bronchitis & emphysema • Air trapping and alveolar destruction promote ventilation/perfusion mismatches, which can result in hypoxia and hypercapnia • Over time, hypoxia can lead to structural changes in the pulmonary vasculature including thickening of the tunica intima and vascular smooth muscle cell hyperplasia • These vascular changes promote pulmonary hypertension which can eventually lead to right sided heart failure (cor pulmonale) and possibly even death • 1/3 of COPD patients suffer from malnutrition COPD Acute exacerbation of COPD (AECOPD) Defined as “acute changes in symptoms beyond what is considered normal variability in a patient”. Half of all hospitalizations in Canada for AECOPD are a result of infections (viral/bacterial). 1/3 for unknown causes. Wedzicha JA & Seemungal T (2007). COPD exacerbations: defining their cause and prevention. Lancet. 370:9589, p786-796. COPD Annual trends (Ontario) Annual trends for ER visits due to AECOP for adults > 40 yrs old cf ER visits due to AE of asthma for adults >= 50 yrs old Neil W. Johnston "The Similarities and Differences of Epidemic Cycles of Chronic Obstructive Pulmonary Disease and Asthma Exacerbations", Proceedings of the American Thoracic Society, Vol. 4, No. 8 (2007), pp. 591-596 COPD Diagnosis • Patient history • Blood gas analysis • Functional lung testing – GOLD definition of chronic obstruction = FEV1/FVC ratio of 0.7 or lower • FEV1 = forced expiratory volume in one second – i.e., volume of air that can be exhaled from the lungs in one second • FVC = forced vital capacity – i.e., maximum volume of air that can be exhaled – FEV1 & FVC decrease, while RV and TLC increase COPD Summary Chronic Bronchitis • Inflammation – – – – Mucus hypersecretion Impaired mucociliary f’n Remodelling of bronchioles Recurrent bacterial infection with inflammation • Productive cough • • Emphysema • Inflammation – Loss of lung elastic tissue (acinus) • • • Little coughing or sputum production Barrel chest Tripod position • Pursed lip breathing Cor pulmonale Polycythemia, Cyanosis Smoking is #1 cause. Expiratory flow limitation (dec. FEV1, inc. RV, inc. TLC). Gas trapping with hyperinflation > increased work of breathing, increased energy expenditure, but decreased energy intake coupled with hypoxemia. Dyspnea, exercise intolerance, muscle wasting, fatigue. [ Chronic Bronchitis and Emphysema often occur together ] Asthma-COPD Overlap Syndrome • Some patients exhibit features of both Asthma and COPD • Proposed definition: “AsthmaCOPD overlap is characterized by post bronchodilator airflow limitation that is not fully reversible, in symptomatic patients with risk factors for COPD and who have clinical features of both asthma and COPD.” (CTS, 2017) • Requires personalize approach to treatment / management Alexandru C et.al. (2021) Asthma-COPD Overlap: A more Simplistic Approach, Current Respiratory Medicine Reviews; 17(2) Lung Cancer RESPIRATORY DISORDERS Lung Cancer Statistics • Global Statistics (WHO, 2022) – Highest mortality (1.8 million deaths) and is second in terms of new cancer cases • Canadian Statistics (CCS, 2022) – Most diagnosed cancer (second to non-melanoma skin cancer) – Represents ~13% of all new cancers – Leading cause of death from cancer for both males and females in Canada (~24% of all cancer deaths) Lung Cancer Risk factors • Smoking is #1 – it is a well-known carcinogen – 10-15% of active smokers develop lung CA • Air pollution • Occupational hazards – Exposure to asbestos, arsenic, chromium, nickel, ionizing radiation, etc. • Genetics – Polymorphisms in genes for growth factors, angiogenesis, apoptosis, DNA repair and detoxification of smoke • Oncogenes & Tumor suppressor genes (p53) • CYP1A1 gene in smoking populations Lung Cancer Classifications • Two major classifications: – Non-small Cell Lung Cancer (~85% of lung CA) – Neuroendocrine Tumors (~15% of lung CA, 25% lung CA deaths) • NSCLC further subdivided into: – Squamous-cell carcinoma (~30% of lung CA) – Adenocarcinoma (~35-40% of lung CA) – Large-cell carcinoma (~10% of lung CA) Lung Cancer Squamous cell carcinoma & Adenocarcinoma • Squamous Cell Carcinoma (NSCLC) – Located near hila, can project into bronchi – Symptoms of non-productive cough or hemoptysis common – increased risk of pneumonia – Tend to remain well localized and metastasize (late) • Adenocarcinoma (NSCLC) – Peripherally located in lung parenchyma – Often asymptomatic, but can present with pleuritic pain – Typical adenoma transition (hyperplasia > carcinoma in situ > minimally invasive > invasive carcinoma) – Strong association with previous smoking, but most common lung CA in those that have never smoked – Other risks: occupational carcinogens, viruses, hormones, family Hx – EGFR+ treated with tyrosine kinase inhibitors Lung Cancer Squamous cell carcinoma & adenocarcinoma Squamous cell carcinoma (NSCLC) • Slow growth rate • Central location • Metastasize late Adenocarcinoma (NSCLC) • • • • Slow/moderate growth rate Peripheral location Metastasizes early Most common in non-smokers Lung Cancer Large-cell carcinoma & Neuroendocrine tumors • Large-cell carcinoma (NSCLC) – Commonly arise centrally (distort trachea & carina) – Tumour cells are large and undifferentiated – Grow rapidly, metastasize early - poor prognosis with metastasis • Neuroendocrine tumor (small cell carcinoma) – Most located centrally (hilar / mediastinal) – Metastasize very early (mediastinum, lymph nodes, brain, BM) – Arise from pulmonary neuroendocrine cells • Cells containing neurosecretory granules responsible for making neurotransmitters, growth factors, and vasoactive substances • Neoplastic syndromes often first signs / symptoms of cancer – Genetic abnormalities in bronchial cells • Deletion of chromosomes, activating oncogenes, inhibiting tumour suppressor genes Lung Cancer Large cell carcinoma & neuroendocrine tumours Large cell carcinoma (NSCLC) Rapid growth rate Cells are undifferentiated Central location Diagnosis by exclusion (other NSCLC ruled out) • Metastasize early and widespread • • • • Neuroendocrine tumour (SCLC) • • • • • Very rapid growth rate Often arise peripherally Metastasizes very early Paraneoplastic syndromes Strongest correlation to smoking Tuberculosis, RSV, Pneumonia RESPIRATORY INFECTIONS Tuberculosis Epidemiology • Infection caused by the bacillus Mycobacterium tuberculosis • Leading cause of death from curable infectious disease worldwide • Global statistics (WHO, 2022) – Estimated 10.6 million people fell ill with TB in 2021 – Most new TB cases occurred in South-East Asia, Africa and the Western Pacific – While mortality related to TB has declined since 2000, a slight increase was observed in 2020 and 2021 (1.6 million in 2021) – 89% of mortalities occurring in African and South-East Asia regions • Canadian statistics (PHAC, 2021) – Incidence of active TB has remained unchanged for the last decade – National incidence of active TB is 5/100,000 (no sex differences) • Highest incidence of active TB in 25-34 age group, followed by 65+ age group – Disproportionately impacts peoples experience social inequities • Incidence among Indigenous peoples is the highest (Inuit 135, FN 16, Metis 2) followed by persons born outside Canada (13.4/100,000) – 5% of those with TB died in 2020 Tuberculosis Overview • TB is highly contagious and transmitted through airborne droplets • Risk factors for the spread of TB include: – Emigration of infected individuals – Crowded settings (institutions, living) – Homelessness – Substance use – Lack of access to screening and care. Tuberculosis Host response to infection Immunocompetent individuals • • • • • • M. tuberculosis contained by inflammatory and immune response system. Results in latent TB infection (LTBI) with on evidence of disease. Inspired bacilli lodge in upper lobes of the lungs; can also migrate to lymph nodes Alveolar macrophages & neutrophils engulf bacilli – macrophage release interferon Bacterium can resist lysosomal killing in macrophages Body attempts to isolate bacilli by forming granulomatous lesion (tubercle) • • Infected tissue in tubercle dies = caseation necrosis (cheese-like material) Tubercule surrounded by collagen, walling off bacilli – response takes 10 days LTBI may last the lifetime of the host Impairment of the immune system can lead to reactivation and progression of disease • • Tuberculosis Clinical manifestations • LTBI is asymptomatic and non-contagious • Active TB – Symptoms develop gradually and may include: • Night sweats, fatigue, weight loss, lethargy, anorexia (loss of appetite) and low-grade fever (afternoon) • Cough with purulent sputum develops and increases in frequency over weeks to months • Dyspnea, chest pain and hemoptysis with disease progression • Extrapulmonary TB can occur in immunocompromised individuals Tuberculosis Evaluation and treatment • Latent TB infection – Tuberculin skin test (TST) • Positive PPD is not sensitive or specific for TB infection – BCG vaccine = false positive – Immunocompromised = false negative – Interferon-gamma release assay (IGRA) • Active TB disease – Chest x-ray, sputum microscopy, mycobacterial culture and drug sensitivity testing, and nucleic acid amplification testing • • X-ray of current or previous active TB will show nodules, calcifications, cavities and hilar enlargement of upper lobes Culture can take up to 6 weeks – necessary for Dx – Individuals with active TB should isolate (until negative sputum result achieved) – Four antibiotic combo to Tx infection – adherence to prevent development of drug resistant strains Radiograph of cavitating – Preventing reactivation of LTBI with anti-tuberculous medication TB lesion is recommended for at-risk individuals Tuberculosis Evaluation and treatment Canadian Tuberculosis Standards - 8th Edition – Canadian Journal of Respiratory, Critical Care, and Sleep Medicine (2021) https://www.tandfonline.com/toc/ucts20/6/sup1 Respiratory Syncytial Virus General information • Enveloped virus, single-stranded RNA • A common lower respiratory tract infection in children – Responsible for 50%-90% of hospitalizations for bronchiolitis, ~25% for pneumonia – A common etiologic agent of croup (most common is parainfluenza virus) • No vaccine • Prophylaxis (palivizumab) in some groups (e.g., premature infants < 32 weeks) during RSV season Azzari, C., et al. Epidemiology and prevention of respiratory syncytial virus infections in children in Italy. Ital J Pediatr 47, 198 (2021). https://doi.org/10.1186/s13052-021-01148-8 Pneumonia Overview • Lower respiratory tract infection, caused by bacteria, viruses, fungi, protozoa, or parasites • Broadly classified as community or hospital acquired • Most common etiologic agent is S. pneumoniae (CAP), P. aeruginosa (HAP), P. carinii (immunocompromised) • Pathogen passes defenses in the upper airway to reach the lower airway • Alveolar macrophages are first point of contact – Recognize pathogens using surface receptors (Toll-like) – Release proinflammatory cytokines TNF-alpha, IL-1, etc. – Promotes influx of other inflammatory cells (neutrophils) • Airway epithelium can recognize some pathogens Pneumonia Pathophysiology • Alveolar macrophages and neutrophils engulf and destroy pathogens using proteilytic enzymes, antimicrobial proteins, and reactive oxygen species. • The ensuing inflammatory response leads to deposition of infectious debris, exudate, fibrin, and edematous fluid in the alveoli. • Accumulation of these substances in the acinus leads to dyspnea, V/Q mismatch, and hypoxemia. Pneumonia Bacterial pneumonia • Complications are common with bacterial pneumonia: – Pleuritis, which may resolve or leave fibrous thickening or permanent adhesions – Empyema (pus in pleural cavity) – Tissue destruction and necrosis, which may lead to abscess formation – Fibrous scarring within lung tissue (decrease lung compliance) – Bacterial spread (heart, brain, kidneys, joints) Thank you!