Upper and lower airway infections Semmelweis University First Department of Medicine Dr. Szathmári Miklós 01. February 2010.

The most common airway infections Common cold Acute pharyngitis Acute bronchitis Chronic obstructive lung disease Pneumonias Community aquired pneumonia Health care associated pneumonia Ventilator associated pneumonia Hospital aquired pneumonia

The common cold in adults Most frequent benign self-limited acute illness (syndrome) caused by members of several families of viruses The term refers to a mild upper respiratory viral illness involving, to variable degrees, sneezing, nasal congestion and rinorrhea, sore throat, cough, low grade fever, headache and malaise The average incidence of the common cold is two to three per year by adulthood

The common cold in adults Rhinoviruses are the most common viruses associated with cold symptoms. Coronaviruses cause 10-15%, influenza virus cause 5-15%, and parainfluenza and RSV virus are responsible for about 5 % Influenza and parainfluenza tipically cause more symptoms than other cold viruses. Seasonal pattern: Rhinovirus, parainfluenza: in fall and late spring RSV and coronavirus in winter and spring Enteroviruses: in the summer Adenoviruses: outbreaks in military facilities, and hospital wards.

The common cold in adults Transmission: hand contact (direct and indirect contact with a contaminated environmental surface. Cold inducing viruses may remain viable on human skin for at least two hours. Droplet transmission is the most common means of transmission for influenza viruses.

The common cold in adults clinical features and pathogenesis Incubation period for most common cold viruses is 24 to 72 hours. The symptoms vary from patient to patient: rhinitis and nasal congestion are most common. The sore throat is frequently the most bothersome symptom on the first day of illness, but it is usually short lived. Cough becomes troublesome on the fourth or fifth day of illness. Nasal discharge may appear to be purulent in the absence of a secondary bacterial infection. Fever is uncommon in adults. Risk factors for increased severity of disease include: Chronic disease Congenital immundeficiency disorders Malnutrition Cigarette smoking

The common cold in adults Complications Sinusitis: viral sinusitis occurs more frequently than secondary bacterial sinusitis Lower respiratory tract disease: Viral upper respiratory infections (rhinovirus) have been linked to up to 40 percent af acute asthma attacks in adults. The increased airway hyperreactivity (may explain the persistent cough following upper respiratory tract infections) can be a consequence of: Local viral infection of lower airway epithelial cells, or Inflammatory mediators acting distantly in the lower airways Otitis media (Eustachian tube dysfuction; impaired clearance and pressure regulation)

Acute pharyngitis One of the most common conditions encountered in office practice. The major treatable pathogen, group A Streptococcus is the cause of pharyngitis in only 10 percent of adults who seek medical care. The vast majority of patients receive antibiotic therapy. The overtreatment of acute pharyngitis represents one of the major causes of antibiotic abuse. Acute rheumatic fever, an important complication af acute streptoccoccal pharyngitis, has nearly disappeared from the most developed countries.

Common causes of acute pharyngitis Pathogens Frequency Examples Viruses 50% Rhinovirus, Adenovirus, Influenza A and B, Parainfluenza, Coxsackievirus, Coronavirus, Echovirus Primary pathogens 10-15% Group A Streptococcus Group C Stretococcus Group G Streptococcus Neisseria gonorrheae Possible primary pathogens <5% Chlamidophilia pneumoniae Mycoplasma pneumoniae Archanobacterium haemolyticum No microbe identified Appr.30%

Identifying group A streptococcal pharyngitis Clinical prognostic score (sensitivity and spesificity range from 55-75%, respectively. Centor criteria: Tonsillar exudates Tender anterior cervical adenopathy Fever by history Absence of cough Diagnostic tests Rapid streptococcal antigen test (RSAT)- ELISA method with 80-90% sensitivity and 90-100% specificity Throat culture (low sensitivity, time delay in obtaining actionable result) Antistreptolysin titer (peak value within two to three weeks. Critical for the diagnosis of acute rheumatic fever but is not helpful for management of streptococcal pharyngitis

Acute bronchitis (etiology) The usual causes of acute bronchitis are viral infections of the upper airways including influenza A and B, parainfluenza, coronavirus, rhinovirus, respiratory syncytial virus, and human metapneumovirus. Bacterial pathogens that cause pneumonia, such as Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis do not cause acute bronchitis, with exception of patients with airway violations such as tracheostomy or endotracheal intubation, or those with exacerbations of chronic bronchitis. Influenza, as the cause of acute bronchitis merits special consideration because of its morbidity and potential for specific therapy. It is treatable with neuroaminidase inhibitors, although these drugs must be given within 48 hours of symptoms onset for demonstrable clinical benefit. Other pathogens: Mycoplasma pneumoniae, Chlamydophila pneumoniae, Bordatella pertussis

Acute bronchitis (clinical symptoms) Self-limited inflammation of the bronchi Clinical sypmtoms: cough, usually with sputum production, and evidence of concurrent upper airway infection. Fever is unusual sign, when accompannying cough, suggest either influenza or pneumonia. The cough often lasts from 10 to 20 days. Purulent sputum in 50% of patients, this usually represents sloughing of cells from the tracheobronchial epithelium, along with inflammatory cells, and does not signify bacterial infection, as is often assumed. The patient often have significant bronchospasm. Airway hyperreactivity improves over five to six weeks.

Acute bronchitis (diagnosis and treatment) Diagnostic tests: In case of abnormal vital signs (fever, tachypnoe, tachycardia) – chest X-ray – diff. diag. Penumonia. Over 75 years of age the patient may have pnemonia with normal vital signs. Microbiology: in patients with severe paroxysmal cough should be evaluated for pertussis regardless of the immunization history Diagnostic studies for mycoplasma and C. pneumoniae Rapid tests for the diagnosis of influenza Bacterial cultures of expectorated sputum in patients with negative chest X-ray are not recommended. Treatment: Symptomatic treatment using nonsteroidal antiinflammatory drugs and nasal decongestants. The patients with acute bronchitis do not have benefit from antibiotic treatment, except patients with serious preexisting comorbidity). Pertussis can be treated with macrolide antibiotic

Chronic obstructive pulmonary disease (COPD) Definition: a disease state characterized by airflow limitation that is not fully reversible. COPD includes Emphysema: destruction and enlargement of lung alveoli Chronic bronchitis: a clinically defined condition with chronic cough and phlegm Small airway disease: a condition in which small bronchioles are narrowed

COPD risk factors The causal relationship between cigarette smoking and the development of COPD has been absolutely proved, Although pack-years of cigarette smoking is the most significant predictor of FEV1, only 15% of the variability in FEV1 is explained by pack-years. Airway responsiveness: increased bronchocontriction in response to a variety of exogenous stimuli Respiratory infections: important causes of exacerbations of COPD, but the association of infections to the development and progression of COPD remains to be proven Occupational exposures: Several specific occupational dusts and fumes are likely risk factors for COPD, the magnitude of these effects appears to be less important than the effect of smoking Ambient air pollution: The prevalence of COPD in urban areas is higher than in the rural areas in connection with the increased pollution in the urba settings. Genetic considerations: Alfa-1 antitrypsin deficinecy (frequency appr. 1% in Caucasian populations)

COPD clinical presentation History The three most common symptoms in COPD: cough, sputum production and dyspnea The development of airflow reduction is a gradual process Activities involving significant arm work, particularly at or above shoulder level, are particularly difficult for patients with COPD. The activities that allow the patient to brace the arms and use accessory muscles of respiration are better tolerated (pushing a shopping cart, walking on a treadmill)

COPD clinical presentation Physical findings In the early stage entirely normal In patients wth more severe disease: prolonged exspiratory phase and exspiratory wheezing. Signs of hyperinflation of the lung: barrel chest, poor diaphragma excursion, use of accessory respiratory muscles, cyanosis. Systemic wasting, significant weight loss, loss of subcutaneous adipose tissue Clubbing of the digits: not a sign of COPD. Development of lung cancer is the most likely explanation for newly developed clubbing

COPD clinical presentation Laboratory findings Spirometry : airflow obstruction with decreased FEV1 and FEV1/FVC. Increased total lung capacity, functional residual capacity and residual volume Arterial blood gases and oximetry: hypoxaemia, Pco2 increased. Elevated hematocrit suggest present of chronic hypoxemia Testing for α1AT deficiency Radiographic evaluation: may assist in the classification of the type of COPD. Obviuos bullas, paucity of parenchymal markings, or hyperlucency suggest emphysema

Influence the natural history of patients with COPD COPD treatment Smoking cessation Oxigen therapy Lung volume reduction surgery Inhaled glucocorticoids Bronchodilatators Anticholinerg agents (tiotropium) Βeta-agonist (long-acting inhaled salmeterol) Theophyllin N-acetyl cysteine α1AT augmentation therapy Antibiotic Influence the natural history of patients with COPD Improve symtoms and decrease of the frequency and severity of exacerbations

COPD antibiotic treatment Patients with COPD are frequently colonized with potential respiratory pathogens, include Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. In addition Mycoplasma pneumoniae and Chlamydiphila pneumoniae are found in 5-10% of exacerbations. The choice of antiobiotic should be based on local patterns of antibiotic susceptibility of these pathogens.

Community aquired pneumonia Definition: an acute infection of the pulmonary parenchyma in a patient who has acquired the infection in the community, as distinquished from Hospital-acquired (nosocomial) pneumonia Healthcare-associated pneumonia (nursing homes, dialysis center, outpatient clinics or within 90 days of discharge from an acute or chronic care facility.

Community aquired pneumonia Clinical features include: Cough and sputum Mucopurulant sputum in association with bacterial pneumonia. Scant and watery sputum in case of atypical pathogen Fever Chills in 40 to 50%. Frequently absent in older patients Pleuritic chest pain in 30% of causes Dyspnea and tachypnoe in 45 to 70% of patients, and may be the most sensitive sign in elderly patients Nausea, vomiting, diarrhea

Community aquired pneumonia (radiologic evaluation) Chest X-ray examination Radiographic appearence may include lobar consolidation, interstitial infiltrates, and/or cavitation If the clinical evaluation does not support pneumonia in a patient with an abnormal chest x-ray, other causes must be considered, such as malignancy, hemorrhage, pulmonary edema, pulmonary embolism, etc. If the clinical syndrome favors pneumonia but the radiograph is negative, the radiograph may represent a false negative result (volume depletion may produce an initially negative radiograph) CT scanning (not generally recommended for routine use)

Community aquired pneumonia (diagnostic testing for microbial etiology) Testing for a microbial diagnosis is usually not performed in outpatients because empiric treatment is almost always succesful. Patients with severe CAP requiring ICU admission should have blood cultures, urinary antigen tests, and sputum culture Some microbes are critical to detect because they represent important epidemiologic challenges and/or serious conditions that require treatment different from standard empiric regimen Legionella, Influenza A and B, community-associated methicillin-resistant Staphylococcus aureus, and agent of bioterrorism (Bacillus anthracis, Yersinia pestis, Francisella tularensis, Coxiella burnetti, Legionella spp, Influenza virus, Hantavirus, and ricin)

Microbial causes of community aquired pneumonia, by site of care Hospitalized patients Outpatients Non-ICU ICU Streptococcus pneumoniae Mycoplasma pneumoniae Haemophilus influenzae Chlamidophila pneumoniae Respiratory viruses S.pneumoniae M. pneumoniae C. pneumoniae H. Influenzae Legionella spp. S. Pneumoniae Staphylococcus aureus Gram-negative bacilli H. influenzae Harrison’s: Principles of Internal Medicine 17th edition. McGraw-Hill

Epidemiologic factors suggesting possible causes of CAP Possible pathogens Alcoholism S. pneumoniae, oral anaerobs, Klebsiella pneum., Mycobacterium tuberculosis, Acinetobacter COPD/smoking Haemophilus inf, Pseudomonas, Legionella, S. pneum, Moraxella catarr. Bronchiectasia, structural lung disease Pseudomonas aer., Staphylococcus aureus Dementia, stroke Oral anaerobs, gram-negative enteric bacteria Lung abscess Staphylococcus aureus, oral anaerobs, endemic fungi, Mycobacterium tuberculosis Stay in hotel or on cruise ship in previous 2 weeks Legionella spp. Local influenza activity Influenza virus, S. pneumoniae, S. aureus Exposure to birds Chlamidophila psittaci Exposure to rabbits Francisella tularensis

Empirical antibiotic treatment of CAP Outpatients Previously healthy and no antibiotic treatment in past 3 months A macrolide or doxycyclin (not in Hungary) or amoxicillin/clavulanate Comorbidities or antibiotics in past 3 months A respiratory fluoroquinolone p.o. or β-lactam + macrolide Inpatients Respiratory fluroquinolone p.o. or iv., or β-lactam + macrolide Special concerns Pseudomonas is a consideration (antistreptococcal, antipseudomonas β-lactam (piperacillin/tazobactam, imipenem plus ciprofloxacin or levofloxacin CA.MRSA is a consideration: add linezolid or vancomycin iv.

Health care-associated pneumonia (ventilator associated pneumonia, VAP) Pneumonia is a common complication among patients requiring mechanical ventilation (the cumulative rate among patients who remain ventilated for as long as 30 days is as high as 70%) Potential etiologic agents include both MDR (multidrug-resistant) and non-MDR bacterial pathogens. The non-MDR pathogens are identical to the pathogens found in severe CAP. Such pathogens predominates if VAP develops in the first 5-7 days of the hospital stay The relative frequency of MDR pathogens vary significantly from hospital to hospital (meany hospital have problems with Pseudomonas aeruginosa and MRSA)

Empirical treatment of HCAP/VAP Patient without risk factors for MDR pathogens: Iv. ceftriaxon or respiratory fluoroquinolone or amoxicillin-clavulinic acid or Ertapenem Patients with risk factors for MDR pathogens: A β-lactam (cetazidine or piperacillin/tazobactam or meropenem) plus a second agent active against gram-negative bacterial pathogens (gentamycin, amikacin, cipro- or levofloxacin) plus an agent active against gram positive bacterial pathogens (Linezolid or Vancomycin)

Hospital-acquired pneumonia (HAP) The HAP in nonintubated patient is similar to VAP Higher frequency of non-MDR pathogens and the better underlying host immunity in non-intubated patients allows monotherapy in a larger proportion of cases HAP than of VAP. The anaerob infection is more common in the non-VAP population Greater risk of macroaspiration Lower oxygen tension in the lower respiratory tract Because of the better host defenses, lower mortality rate than in VAP