Pneumonia

Learning Objectives

• To be aware of Pneumonias. • Defining pneumonia. • To be able to describe pathophysiology of pneumonia • Able to classify the different types of pneumonia. • To identify the factors that predispose to pneumonia. • Describe different microorganisms causing pneumonia. • Able to describe clinical features of pneumonia. • To be familiar with the investigations required to diagnose pneumonia. • Should be able to discuss differential diagnosis of pneumonia. • Describe the different complications of pneumonia.

Introduction

• The term pneumonia is used to describe inflammation of parenchymal structures of the lung, such as the alveoli and the bronchioles.

• It is usually caused by infection with viruses or bacteria and less commonly other microorganisms or other conditions such as autoimmune disease

• Noninfectious causes such as inhalation of irritating fumes or aspiration of gastric contents, although much less common than infectious causes, can result in severe pneumonia.

What is Pneumonia ?• Pneumonia is as an acute respiratory illness associated with recent onset

radiological pulmonary shadowing which may be involve one or more lung segments or lobes (segmental, lobar or multilobar).

• As a result of inflammation, protein rich fluid and inflammatory cells congest the airspaces, leading to histo-pathological changes. This is called as consolidation of lung tissue.

Gross pathology in pneumonia

Impaired gas exchange in pneumonia

Classification of Pneumonias

• Pneumonias can be commonly classified according to

1) The type of agent (typical or atypical) causing the infection,

2) Distribution of the infection (lobar pneumonia or bronchopneumonia), and

3) Setting (community or hospital) in which it occurs. Persons with compromised immune function constitute a special concern in both categories.

Classification of Pneumonias

Typical pneumonias result from infection by bacteria that multiply extracellularly in the alveoli and cause inflammation and exudation of fluid into the air-filled spaces of the alveoli

Atypical pneumonias are caused by viral and mycoplasma infections that involve the alveolar septum and the interstitium of the lung. They produce less striking symptoms and physical findings than bacterial pneumonias

Acute bacterial pneumonias can be classified as lobar pneumonia or bronchopneumonia, based on their anatomic pattern of distribution In general, lobar pneumonia refers to consolidation of a part or all of a lung lobe, and bronchopneumonia signifies a patchy consolidation involving more than one lobe

Epidemiology

• Pneumonia is a common illness affecting approximately 450 million people a year and occurring in all parts of the world.

• It is a major cause of death among all age groups resulting in 4 million deaths (7% of the world's total death) yearly.

• Rates are greatest in children less than 5 years, and adults older than 75 years.

• Community-acquired pneumonia (CAP) figures from developed countries suggest that an estimated 5-11/1000 adults suffer from CAP each year, accounting for around 5-12% of all lower respiratory tract infections.

Factors predisposing to pneumonia

• Cigarette smoking• Upper respiratory tract infections• Alcohol• Corticosteroid therapy• Old age• Recent influenza infection• Pre-existing lung disease• HIV• Indoor air pollution

DEFENSE MECHANISM FUNCTION FACTORS THAT IMPAIR EFFECTIVENESS

Glottic and cough reflexes Protect against aspiration into tracheo- bronchial tree

-Loss of cough reflex due to stroke or neural lesion, neuromuscular disease, abdominal or chest surgery,

-Depression of the cough reflex due to sedation or anesthesia, presence of a nasogastric tube

Muco-ciliary blanket Removes secretions, microorganisms, and particles from the respiratory tract

Smoking, viral diseases, chilling, inhalation of irritating gases

Phagocytic and bactericidal action of alveolar macrophages

Removes microorganisms and foreign particles from the lung

Tobacco smoke, chilling, alcohol, oxygen intoxication

Immune defenses (IgA and IgG and cell-mediated immunity)

Destroy microorganisms Congenital and acquired immunodeficiency states

Factors predisposing to pneumonia

Clinical presentation of pneumonia• Pneumonia usually presents as an acute illness with respiratory and systemic features

• Pulmonary symptoms include breathlessness and cough

• Initially the cough is characteristically short, painful and dry, but later accompanied by the expectoration of mucopurulent sputum.

• Rust-coloured sputum may be seen in patients with Strep. pneumoniae infection, and some patients may report hemoptysis.

• Pleuritic chest pain may be a presenting feature and on occasion may be referred to the shoulder or anterior abdominal wall.

Clinical presentation of pneumonia

• Systemic features include : fever, rigors, shivering, vomiting, reduced appetite and headache.

• Less typical presentations may be seen in very young and very old patients.

• Clinical signs reflect the nature of the inflammatory response. This improves the conductivity of sound to the chest wall and the clinician may hear bronchial breathing and whispering pectoriloquy . Crackles are often also detected.

Objectives of the Investigations for Pneumonia

• The objectives are to :

1) Exclude other conditions that may present in a similar manner to pneumonia

2) To assess the severity

3) Identify the development of complications

Investigations

• A chest X-ray usually provides confirmation of the diagnosis.• In lobar pneumonia, a homogeneous opacity localised to the affected lobe or segment

usually appears within 12-18 hours of the onset of the illness • Chest X-ray is also useful if a complication such as parapneumonic pleural effusion,

intrapulmonary abscess formation or empyema (pus in the pleural cavity) is suspected

Investigations

• Pulse oximetry provides a non-invasive method of measuring arterial oxygen saturation (SaO2) and monitoring response to oxygen therapy.

• An arterial blood gas is important in those with low SaO2 or with features of severe pneumonia, to identify ventilatory failure or acidosis.

Pulse Oximetry99 % Oxygen saturation

85 beats per minute Pulse rate

Investigations

• The white cell count may be raised in bacterial pneumonias but normal or only slightly raised in pneumonia caused by atypical organisms (eg Klebsiella, Mycoplasma, Chlamydia)

• Renal function, serum electrolytes and liver function tests should also be checked.

• The C-reactive protein (CRP) (a marker of acute inflammatory/infective process) is typically elevated.

Investigations to assess severity of pneumonia

• A very high (> 20 × 109/l) or low (< 4 × 109/l) white cell count may be seen in severe pneumonia and is therefore an indicator of severity.

• Renal function, serum electrolytes and liver function tests should also be checked and derangement may indicate severe disease.

• Ongoing or worsening clinical status and Respiratory failure (Hypoxia with or without CO2 retention) may indicate severity of the disease

• Pneumonia severity scores may be used to assess the degree of severity

Investigations to assess severity of pneumonia

• The CURB-65 scoring system helps guide antibiotic and admission policies, and gives useful prognostic information.

Identification of the organism in patients with severe CAP

• A full range of microbiological tests should be performed on sputum and blood samples of patients with severe pneumonia.

• In patients who do not respond to initial antibiotic therapy, microbiological results may allow its appropriate modification.

• Microbiology also provides useful epidemiological information.

Streptococcus pneumoniae (Pneumococcus/ Diplococcus)

in sputum

Microbiological investigations in patients with CAP

• For all patients

• Sputum: direct smear by Gram and Ziehl-Neelsen stains. Culture and antimicrobial sensitivity testing

• Blood culture: frequently positive in pneumococcal pneumonia

• Serology: acute and convalescent titres for Mycoplasma, Chlamydia, Legionella, and viral infections. Pneumococcal antigen detection in serum or urine

• PCR: Mycoplasma can be detected from swab of oropharynx

Microbiological investigations in patients with CAP

• For patients with Severe community-acquired pneumonia

• The above tests plus possibly: Tracheal aspirate, induced sputum, bronchoalveolar lavage, protected brush specimen or percutaneous needle aspiration. Direct fluorescent antibody stain for Legionella and viruses

• Serology: Legionella antigen in urine. Pneumococcal antigen in sputum and blood. Immediate IgM for Mycoplasma

• Cold agglutinins: positive in 50% of patients with Mycoplasma

Microbiological investigations in patients with CAP

• Some selected patients may require:

• Throat/nasopharyngeal swabs: helpful in children or during influenza epidemic

• Pleural fluid: should always be sampled when present in more than trivial amounts, ideally with ultrasound guidance

Common differential diagnosis of pneumonia

• Pulmonary infarction (eg due to pulmonary embolism)

• Pulmonary/pleural Tuberculosis

• Pulmonary oedema (eg cardiac failure)

• Malignancy: bronchoalveolar cell carcinoma

Prevention of pneumonia• Current smokers should be advised to stop smoking

• Influenza and pneumococcal vaccination should be considered in selected patients who may be at high risk for disease

• Other measures include: Improving nourishment, and reducing indoor air pollution

• In chldren, immunisation should be encouraged, against measles, pertussis and Haemophilus influenzae type b

A discussion of the common types of Pneumonia

1. Community acquired pneumonia2. Acute Bacterial (Typical) Pneumonia:Pneumococcal pneumonia3. Legionnaire disease4. Primary Atypical Pneumonia5. Hospital acquired Pneumonia6. Suppurative Pneumonia7. Pneumonia in immunocompromised patient

Community-Acquired Pneumonia

• The term community-acquired pneumonia is used to describe infections from organisms found in the community rather than in the hospital or nursing home.

• It is defined as an infection that begins outside the hospital or is diagnosed within 48 hours after admission to the hospital in a person who has not resided in a long term care facility for 14 days or more before admission.

• Community-acquired pneumonia may be further categorized according to risk of mortality and need for hospitalization based on age, presence of coexisting disease, and severity of illness, using physical examination, laboratory, and radiologic findings.

Common organisms causing Community acquired pneumonia (CAP)

• Streptococcus pneumoniae: Most common cause. Affects all age groups, particularly young to middle-aged. Characteristically rapid onset, high fever and pleuritic chest pain; may be accompanied by herpes labialis and 'rusty' sputum. Bacteraemia more common in women and those with diabetes or COPD

• Mycoplasma pneumoniae: Children and young adults. Epidemics occur every 3-4 years, usually in autumn. Rare complications include haemolytic anaemia, Stevens-Johnson syndrome, erythema nodosum, myocarditis, pericarditis, meningoencephalitis, Guillain-Barré syndrome

Common organisms causing Community acquired pneumonia (CAP)

• Legionella pneumophila : Middle to old age. Local epidemics around contaminated source, e.g. cooling systems in hotels, hospitals. Person-to-person spread unusual. Some features more common, e.g. headache, confusion, malaise, myalgia, high fever and vomiting and diarrhoea. Laboratory abnormalities include hyponatraemia, elevated liver enzymes, hypoalbuminaemia and elevated creatine kinase. Smoking, corticosteroids, diabetes, chronic kidney disease increase risk

• Haemophilus influenzae :More common in old age and those with underlying lung disease (COPD, bronchiectasis)

Common organisms causing Community acquired pneumonia (CAP)

• Streptococcus pneumoniae

• Mycoplasma pneumoniae

• Legionella pneumophila

• Haemophilus influenzae

Other organisms causing pneumonia

• Staphylococcus aureus :Associated with debilitating illness and often preceded by influenza. Radiographic features include multilobar shadowing, cavitation, pneumatocoeles and abscesses. Dissemination to other organs may cause osteomyelitis, endocarditis or brain abscesses. Mortality up to 30%

• Chlamydia psittaci : Consider in those in contact with birds, especially recently imported and exotic. Malaise, low-grade fever, protracted illness, hepatosplenomegaly and occasionally headache with meningism

Other organisms causing pneumonia

• Klebsiella pneumoniae (Freidländer's bacillus) : More common in men, alcoholics, diabetics, elderly, hospitalised patients, and those with poor dental hygiene. Predilection for upper lobes and particularly liable to suppurate and form abscesses. May progress to pulmonary gangrene

• Primary viral pneumonias: Influenza, parainfluenza, measles, Herpes simplex, Varicella, Adenovirus, Cytomegalovirus (CMV). Viral pneumonias may be complicated by secondary bacterial infection . Viruses may cause pneumonia in the immunosuppressed such as in malnourished children and immunocompromised adults. SARS (severe acute respiratory distress syndrome) should be suspected if a high fever (> 38°C), malaise, muscle aches, a dry cough and breathlessness follow within 10 days of travel to an area affected by an epidemic

Acute Bacterial (Typical) Pneumonias

• The lung below the main bronchi is normally sterile

• Small amounts of organisms that colonize upper airways, do not normally cause infection because of the small numbers that are aspirated and because of the respiratory tract’s defense mechanisms that prevent them from entering the distal air passages

Acute Bacterial (Typical) Pneumonias

• Loss of the cough reflex, damage to the ciliated endothelium that lines the respiratory tract, or impaired immune defenses predispose to colonization and infection of the lower respiratory system.

• Bacterial adherence also plays a role in colonization of the lower airways. The epithelial cells of critically and chronically ill persons are more receptive to binding microorganisms that cause pneumonia.

Pneumococcal Pneumonia

• Streptococcus pneumoniae (pneumococcus) is the most common cause of bacterial pneumonia.

• It is a gram-positive diplococcus (in pairs), possessing a capsule of polysaccharide.

Streptococcus pneumoniae (Pneumococcus/ Diplococcus)

in sputum

Pathogenesis of typical Pneumococcal Pneumonia

• The initial step in the pathogenesis of pneumococcal infection is the attachment and colonization of the organism to the mucus and cells of the nasopharynx even though perfectly healthy people can be colonized by the organism and may carry the organism without evidence of infection.

• If the host defense is weak and /or there are any predisposing factors for pneumonia, then pneumonia may develop.

Pathological stages of Pneumonia

The pathologic process of pneumococcal pneumonia can be divided into the four stages—edema, red hepatization, gray hepatization, and resolution.

1. Edema: During the first stage of pneumococcal pneumonia, the alveoli become filled with a protein- rich edema fluid containing numerous organisms

2. Red hepatization Marked capillary congestion follows, leading to massive out- pouring of polymorphonuclear leukocytes and red blood cells. Because the consistency of the affected lung at this point resembles that of the liver, this stage is referred to as the red hepatization stage.

Pathological stages of Pneumonia

3. Gray hepatization The next stage, occurring after 2 or more days, depending on the success of treatment, involves the arrival of macrophages that phagocytose the fragmented polymorphonuclear cells, red blood cells, and other cellular debris. During this stage, which is termed the gray hepatization stage, the congestion has diminished but the lung is still firm.

4. Resolution :The alveolar exudate is then removed and the lung gradually returns to normal.

Immunization against Pneumococcal pneumonia • A 23-valent pneumococcal vaccine, composed of antigens from 23 types of S.

pneumoniae capsular polysaccharides, is used

• The vaccine is recommended for persons 65 years of age or older and persons aged 2 to 65 years with chronic illnesses, particularly cardiovascular and pulmonary diseases, diabetes mellitus, and alcoholism

• Immunization also is recommended for immunocompromised persons 2 years of age or older, including those with sickle cell disease, spleenectomy, Hodgkin disease, multiple myeloma, renal failure, nephrotic syndrome, organ transplantation, and HIV infection

Legionnaire Disease

• Legionnaire disease is a form of bronchopneumonia caused by a gram-negative bacillus, Legionella pneumophila.

• Infection normally occurs by acquiring the organism from the environment.

• Infection typically occurs when water that contains the pathogen is aerosolized into appropriately sized droplets and is inhaled or aspirated by a susceptible host eg infected air conditioners or showers

Clinical features and Diagnosis of Legionnaire disease

• Symptoms of the disease typically begin approximately 2 to 10 days after infection

• Onset is usually abrupt, with malaise, weakness, lethargy, fever, and dry cough

• Other manifestations include disturbances of central nervous system function, gastrointestinal tract involvement, arthralgias, and elevation in body temperature, sometimes to more than 104°F

• The presence of pneumonia along with diarrhea, hyponatremia, and confusion is characteristic of Legionella pneumonia

• The disease causes consolidation of lung tissues and impairs gas exchange

Clinical features and Diagnosis of Legionnaire disease

• Diagnosis is based on clinical manifestations, radiologic studies, and specialized laboratory tests to detect the presence of the organism

• Of these, the Legionella urinary antigen test is a relatively inexpensive, rapid test that detects antigens of L. pneumophila in the urine

Primary Atypical Pneumonia

• The atypical pneumonias are characterized by patchy involvement of the lung, largely confined to the alveolar septum and pulmonary interstitium

• The term atypical denotes a lack of lung consolidation, production of moderate amounts of sputum, moderate elevation of white blood cell count, and lack of alveolar exudate

• The agents that cause atypical pneumonias damage the respiratory tract epithelium and impair respiratory tract defenses, thereby predisposing to secondary bacterial infections

Aetiology of Primary Atypical Pneumonias• The primary atypical pneumonias are caused by a variety of agents, the most common

being Mycoplasma pneumoniae.

• Mycoplasma infections are particularly common among children and young adults.

• Other etiologic agents include viruses (e.g., influenza virus, respiratory syncytial viruses, adenoviruses, rhinoviruses, rubeola [measles] and varicella [chickenpox] viruses, and Chlamydia pneumoniae.

• In some cases, the cause is unknown.

Mycoplasma pneumonia

Clinical features of Primary Atypical pneumonias

• The clinical course varies widely from a mild infection to a more serious outcome

• The symptoms usually include fever, headache, and muscle aches and pains

• Cough, when present, is characteristically dry, hacking, and nonproductive

• The diagnosis is usually made based on history, physical findings, and chest X-rays

Hospital-acquired or Nosocomial pneumonia

• Hospital-acquired, or nosocomial, pneumonia is defined as a lower respiratory tract infection that was not present or incubating on admission to the hospital. Usually, infections occur- ring 48 hours or more after admission are considered hospital acquired.

• It is one of the most common hospital-acquired infection (HAI) and the leading cause of HAI-associated death.

• Persons requiring intubation and mechanical ventilation are particularly at risk, as are those with compromised immune function, chronic lung disease, and airway instrumentation, such as endotracheal intubation or tracheotomy.

Hospital-acquired or Nosocomial pneumonia

• Ventilator-associated pneumonia Older people are particularly at risk, as are patients in intensive care units, especially when mechanically ventilated, in which case the term ventilator-associated pneumonia (VAP) is applied.

• Health care-associated pneumonia (HCAP) refers to the development of pneumonia in a person who has spent at least 2 days in hospital within the last 90 days, attended a haemodialysis unit, received intravenous antibiotics, or been resident in a nursing home or other long-term care facility.

Aetiology ofHospital-acquired or Nosocomial pneumonia

• The organisms that are responsible for hospital acquired pneumonias are different from those responsible for community acquired pneumonias, and many of them have acquired antibiotic resistance and are more difficult to treat.

• HAP is more often attributable to Gram-negative bacteria (e.g. Escherichia coli, Pseudomonas and Klebsiella species), Staphylococcus aureus (including methicillin-resistant Staph. aureus (MRSA)) and anaerobes.

• However HAP occurring within 4-5 days of admission (early-onset), can be due to organisms similar to those involved in CAP

Factors predisposing to hospital-acquired pneumonia

Reduced host defences against bacteria • Reduced immune defences (e.g. steroid treatment, diabetes, malignancy)• Reduced cough reflex (e.g. post-operative)• Disordered mucociliary clearance (e.g. anaesthetic agents)• Bulbar or vocal cord palsy

Aspiration of nasopharyngeal or gastric secretions • Immobility or reduced conscious level• Vomiting, dysphagia, achalasia or severe reflux• Nasogastric intubation

Bacteria introduced into lower respiratory tract • Endotracheal intubation/tracheostomy• Infected ventilators/nebulisers/bronchoscopes• Dental or sinus infection

Bacteraemia • I.v. cannula infection

Clinical features that may indicate HAP

• HAP should be considered in any hospitalized or ventilated patient who develops:

1) purulent sputum (or endotracheal secretions), 2) new radiological infiltrates, 3) an otherwise unexplained increase in oxygen requirement, 4) fever and leucocytosis or leucopenia.

Investigations for HAP

• Appropriate investigations are similar to those outlined for CAP

• Whenever possible, microbiological confirmation should be done.

• In mechanically ventilated patients, bronchoscopy-directed protected brush specimens or bronchoalveolar lavage (BAL) may be performed.

• Endotracheal aspirates may be obtained but are less reliable.

Prevention of HAP

• The mortality from HAP is high and prevention is important.

• Good hygiene is important for patients and medical staff and equipment.

• Steps should be taken to minimize the chances of aspiration and improve patients’ oral hygiene

Suppurative pneumonia, aspiration pneumonia and pulmonary abscess

A) Suppurative pneumonia is characterised by destruction of the lung parenchyma by the inflammatory process.

• Microabscess formation is a characteristic histological feature

B) Aspiration pneumonia refers to pneumonia occuring after aspiration of septic material into the respiratory tract eg inhalation of septic material during operations on the nose, mouth or throat, under general anaesthesia, or of vomitus during anaesthesia or coma

• Aspiration pneumonia usually affects the dependent areas of the lung such as the apical segment of the lower lobe in a supine patient.

C) Pulmonary abscess refers to lesions in which there is a large localised collection of pus, or a cavity lined by chronic inflammatory tissue, from which pus has escaped by rupture into a bronchus.

Suppurative pneumonia, aspiration pneumonia and pulmonary abscess

Pulmonary abscess refers to lesions in which there is a large localised collection of pus, or a cavity lined by chronic inflammatory tissue, from which pus has escaped by rupture into a bronchus.

Pulmonary abscess

Clinical features of Suppurative pneumonia

Symptoms • Cough productive of large amounts of sputum which is

sometimes blood-stained and foul smelling• Pleural chest pain (Worse on inspiration, coughing, movement

or lying on the same side as the pneumonia) is common• Sudden expectoration of copious amounts of foul sputum

occurs if abscess ruptures into a bronchus

Clinical features of Suppurative pneumonia

Clinical signs • High remittent pyrexia• Profound systemic upset• Digital clubbing may develop quickly (10-14 days)• Chest examination usually reveals signs of consolidation; signs

of cavitation may be found (eg cavernous bronchial breath sounds)

• Pleural rub (indicating pleura inflammation) common• Rapid deterioration in general health with marked weight loss

can occur if disease not adequately treated

Pneumonia in the immunocompromised patient

• The term ‘immunocompromised’ is applied to persons with a variety of underlying defects in host defenses.

• It may include patients with primary and acquired immunodeficiency states, those who have undergone bone marrow or organ transplantation (and are usually on immunosuppressant drugs), persons with solid organ or hematologic cancers, cancer patients on cytotoxic chemotherapy or patients with acquired immunodeficiency conditions ( eg HIV infection).

Pneumonia in the immunocompromised patient

• Defects in humoral immunity predispose to bacterial infections against which antibodies play an important role, whereas defects in cellular immunity predispose to infections caused by viruses, fungi, mycobacteria, and protozoa.

• Neutropenia and impaired granulocyte function, as occur in persons with leukemia, chemotherapy, and bone marrow depression, predispose to infections caused by S. aureus, Aspergillus, gram- negative bacilli, and Candida.

• A fulminant pneumonia usually is caused by bacterial infection, whereas an insidious onset usually is indicative of a viral, fungal, protozoal, or mycobacterial infection.

Summary• Pneumonias are respiratory disorders involving inflammation of the lung structures, such as the alveoli and

bronchioles

• Pneumonia can be caused by infectious agents and noninfectious agents (such as aspirated gastric secretions)

• Pneumonias due to infectious agents commonly are classified according to the source of infection (community acquired or hospital acquired) , part of the lung involved (segmental, lobar, multilobar) and according to the immune status of the host (pneumonia in the immunocompromised person)

• Clinically pneumonias may present with typical or atypical features involving the respiratory system as well as systemic features

• Pneumonias may lead to complications that may be fatal

• Investigations for pneumonia commonly include sputum and blood testing, Chest radiography and microbiological studies

• Treatment of Pneumonia depends on the likely type of pneumonia and causative factor

• Prevention of pneumonias through vaccines and other general health measures is strongly advised, especially in persons who are prone to developing pneumonia.