Lower Respiratory

Tract infections
Nankya Allen Rhoda
Moderator: Dr Sendagire Hakim
Lower respiratory tract
infections.
• Acute Bronchitis
• COPD and Exacerbations.
• Bronchiolitis
• Acute Pneumonia
• Pleural Effusion and Empyema
• Bacterial Lung abscess
• Chronic Pneumonia
• Cystic fibrosis
Acute Bronchitis
• Acute bronchitis refers to a clinical syndrome characterized by a
relatively brief, self-limited inflammatory process of large and
midsized airways
• It is not associated with pneumonia on chest radiograph.
• It is characterized by a dry or productive cough of less than 3 weeks’
duration.
• It is most prevalent in winter, and is primarily caused by viruses.
Microbial Etiology
• It is thought to be most commonly caused by a wide range of viruses
• 10% of cases are attributed to bacterial pathogens ie Mycoplasma
pneumoniae, Chlamydophila pneumoniae, and Bordetella pertussis.
• Cases caused by different pathogens varies according to age,the
season studied and diagnostic methods used.
• Molecular tests, rather than standard culture, identify a greater
number and wider range of viral pathogens.
Pathogenesis
• A combination of direct cytopathology of the pathogen and host immune
response.
• Varies for each of the viruses, the location and extent of cytopathology in
the airways also varies.
• Histopathologic changes in the airways during infection are best
characterized for influenza virus.
• In a recent autopsy series of 47 children with fatal influenza; submucosal
congestion, hemorrhage, mononuclear cell infiltration, and epithelial
necrosis were noted in 50% of cases.
• Similar findings have been reported in adults, along with occlusion of
airways by desquamated necrotic debris.
• In less severe influenza, bronchoscopic examination reveals only mild
inflammatory changes.
• RSV has also been demonstrated to infect terminal bronchiolar lining
cells with extensive debris occluding the lumen in infants, but similar
data are lacking in adults.
• Rhinovirus, which is primarily associated with URT common cold
symptoms, produces patchy infection of bronchial epithelial cells.
• The innate immune response is xterised by virus-induced release of
proinflammatory cytokines and chemokines by respiratory epithelial
cells and immune cells, contributes to systemic and local symptoms.
• Early after infection with influenza, type I interferons, TNF, and IL-6
can be detected.
• B. pertussis is unique in that its expression of toxins may play a role in
clinical symptoms, including the prolonged characteristic cough.
Clinical Presentation
• In most children and adults, acute bronchitis begins with symptoms
typical of the common cold syndrome. Nasal congestion, rhinitis, sore
throat, malaise, and low-grade fever.
• This is followed by the onset of cough, which becomes the dominant
symptom in acute bronchitis.
• In mild cases, the illness last only 7 to 10 days whereas in others,
cough may persist for up to 3 weeks or longer.
• Wheezing is common with acute bronchitis.
• In one study from the Netherlands, 37% of patients with acute
bronchitis ultimately were diagnosed with asthma..
• Host factors ie age, underlying medical conditions, immune status,
environmental factors eg second-hand smoke exposure, can influence
clinical presentation and illness severity.
• Older patients and those with underlying cardiopulmonary remain ill
for an average of 16 to 17 days in contrast to younger persons whose
illness lasts an average of 7 to 10 days.
• In M. pneumoniae infection, cough can be particularly persistent and
irritating, often with minimal phlegm, causing severe chest discomfort
Diagnosis
• It should be suspected in any person with an acute respiratory illness in
which cough is the dominant complaint.
• History including underlying COPD or asthma, travel history, exposure to
environmental irritants, prolonged cough .
• Physical examination should be attentive to signs of pneumonia, to
discriminate acute bronchitis from pneumonia.
• Standard lab tests ie CBC and serum C-reactive protein, do not reliably
discriminate viral from bacterial infection.
• Serum procalcitonin level below 0.1 ng/mL may be a more reliable indicator
of patients with a variety of acute respiratory syndromes, including acute
bronchitis, that do not require antibiotic therapy
• Rapid antigen detection in nasopharyngeal swabs is relatively
sensitive for influenza virus in all age groups and RSV in infants.
• Identification of other viral pathogens requires tissue culture or
reverse transcriptase–polymerase chain reaction (RT-PCR) assay.
• Diagnosis of M. pneumoniae rests on demonstrating pathogen-
specific IgM in serum or PCR.
• B. pertussis diagnosis can be made by serology, PCR, or culture
Treatment
• Symptomatic, directed at relief URT symptoms, cough, and wheezing.
• Acute cough is controlled with narcotic cough suppressants,
expectorants, antihistamines, decongestants, and β2-agonists.
• Current guidelines, do not recommend the routine use of antibiotics
for uncomplicated acute bronchitis.
• Even patients with M. pneumoniae or C. pneumoniae infection may
not benefit from macrolides or quinolones in the absence of
pneumonia.
• Early therapy of B. pertussis with macrolides or tetracyclines is
indicated to prevent transmission.
COPD
• Chronic obstructive pulmonary disease (COPD) has been defined by
ATS and ERS as a disease xterized by and diagnosed with spirometric
measurement of airflow limitation that is not fully reversible.
• The “airflow limitation is usually progressive and is associated with an
abnormal inflammatory response of the lungs to noxious particles or
gases.”
Risk factors
• The most frequent risk factor for COPD worldwide is cigarette
smoking
• Deficiency of blood enzyme α1-antitrypsin which is a protease
inhibitor.
• Exposure to air pollution from wood or other biomass fuel burning.
• Genetics, gender, and altitude may constitute additional susceptibility
factors that determine which smokers develop disease and to what
extent
• Other occupational exposures also have been identified as risk
factors for COPD.
Clinical Presentation
• Small airway remodeling and obstruction on one side, and loss of
elastic recoil from emphysema on the other.
• Separating the extreme forms as predominantly emphysema or
predominantly bronchitis, based on clinical and physiologic criteria is
helpful.
• The emphysema-predominant patient typically has more dyspnea,
less sputum, and fewer respiratory infections. The patient is more
likely to be of thin habitus, a barrel chest, diminished breath sounds.
• The bronchitis-predominant patient has more productive cough, is prone
to infections, maintains body weight or is overweight, has lung crackles
and wheezing, and perhaps has right sided heart failure and pedal edema.
• Lethargy or somnolence can develop and acrocyanosis, polycythemia
• Frequent coughing is a characteristic of most patients with advanced
COPD.
• Many patients cough up the largest amount in the morning.
• Sputum may be viscous, sticky, and obviously purulent, with the latter
being a sign of a bacterial infection.
• Nasal or sinus congestion and a postnasal drip often are associated.
Microbes in stable COPD
• Cultures of the bronchial secretions of the lower airways grow
bacteria found in the nasopharynx of healthy individuals, ie
[Link], [Link], [Link]
• In 18 patients with stable COPD,PBC cultures were positive from 83%
with several species of bacteria in 5 patients (H. influenzae or
[Link], 2 of each, and [Link] ).
• Viridans group streptococci, Neisseria spp., Corynebacterium spp.,
and Candida spp.
Viruses in stable COPD
• Viruses were detected in 16.2% of nasal aspirates from 68 patients during a
stable phase of COPD; these included rhinovirus, coronaviruses, RSV and
parainfluenza virus.
• Patients who had viruses detected in their aspirates gave a history of more
frequent exacerbations than patients who had no viruses recovered.
• RSV was detected in 23.5% of 68 stable COPD patients, it represents
asymptomatic infection.
• EBV was identified in sputum samples of 46% of COPD patients in stable
condition but in only 6% of nonobstructed control smokers,.
• There is increased prevalence of COPD in patients who are HIV-positive.
Atypical Bacteria
• The role of [Link] and [Link] in COPD is not clear.
• M. pneumoniae is rarely a cause of exacerbation and C. pneumoniae
is thought to be responsible in only 4% to 5% of cases.
• In stable COPD, almost no isolates of either microbe were detected in
nasal aspirates
• In another study of patients with steady-state chronic bronchitis,
sputum colonization with C. pneumoniae was found in 38% of
patients .
Bronchiolitis
• Bronchiolitis is the most common acute viral LRT illness occurring
during the first 2 years of life.
• The definition usually applies to children younger than 2 years with a
first episode of wheezing commonly associated with fever, cough,
rhinorrhea, and tachypnea.
• Bronchiolitis has been estimated to be the leading cause of all
hospitalizations among infants in the United States.
Epidemiology
• Bronchiolitis shows a yearly seasonal pattern that varies according to
geography and climate.
• In temperate climates, the peak occurrence of cases is during the
winter to early spring, and usually correlates with the prevalence of
RSV in the community.
• Outbreaks of bronchiolitis are less distinctive in warmer and tropical
climates, cases in these areas may be seen throughout the year.
• Bronchiolitis is most common during the first year of life, with the
peak attack rate occurring between 1 and 10 months of age and
among hospitalized cases between 2 and 5 months of age.
Pathophysiology
• In 1940, Engle and Newns carefully described the pathology of a severe
and often fatal LRT disease they observed in infants, they called this
“proliferate mural bronchiolitis.”
• Their findings of the generalized involvement of the respiratory
epithelium of the small airways have been confirmed as being xteristic of
infection-induced bronchiolitis among young children.
• The virus initially replicates in the epithelium of the URT with
subsequent spread within a few days to the LRT.
• Early inflammation of the bronchial and bronchiolar epithelium occurs
along with peribronchiolar infiltration, mostly with mononuclear cells,
and edema of the submucosa and adventitia.
• The respiratory epithelium becomes necrotic and is sloughed into the
lumina of the airways. Subsequently, the epithelium proliferates and
shows cuboidal cells without cilia
• Inflammatory changes of variable severity are observed in most small
bronchi and bronchioles.
• Inflammation and edema make the lumina of small airways in infants
particularly vulnerable to obstruction
• Plugs of necrotic material and fibrin may completely or partially
obstruct the small airways.
Clinical manifestations
• Bronchiolitis commonly has a prodrome of several days that is marked
by URT signs, especially coryza, cough, and fever.
• LRT involvement may be signaled by the development of a prominent
cough, followed by an increased respiratory rate.
• Retractions of the chest wall, flaring of the nasal alae, and grunting
are evidence of increased work of breathing.
• Wheezing or crackles.
• Decreasing lung sounds associated with increasing dyspnea may
indicate progressive obstruction and impending respiratory failure.
• Dehydration commonly accompanies bronchiolitis, resulting from
paroxysms of coughing.
• Tachypnea increases the fluid requirement further.
• The acute course of bronchiolitis typically lasts 3 to 7 days.
• Most infants improve within 3 to 4 days, with a gradual recovery
period of 1 to 2 weeks, but the cough may persist longer.
Complications
• Complications occur mostly in infants within the 1st several months of life; in
premature infants; and in children with chronic cardiac, pulmonary, and
immunodeficiency diseases.
• Progression to respiratory failure is uncommon with currently available
management.
• Apnea occurs in 3% to 21% of infants.
• Apnea typically is the presenting manifestation, but occurs after several days of
respiratory symptoms.
• Aspiration has also been shown to be a frequent complication in infants
hospitalized with RSV bronchiolitis.
• Infants who received no therapy for aspiration were much more likely to develop
reactive airway disease.
Diagnosis
• Laboratory determination of the specific etiology of bronchiolitis
usually is unnecessary because the management would not be altered
in most cases.
• Rapid virologic diagnosis may be useful, however, for the
implementation of appropriate infection control procedures and
cohorting of patients.
• Viral diagnosis also is necessary for determination of specific antiviral
therapy, which currently is limited primarily to children with high-risk
conditions or severe illness with influenza or RSV.
• Rapid viral antigen techniques are most commonly used because of
their ease, cost, and availability of results within hours.
• These include direct and indirect immunofluorescent assays, optical
immunoassays, and enzyme immunoassays.
• These assays are available for RSV, parainfluenza viruses, influenza
viruses, and Hmpv.
• Serologic tests are rarely helpful in clinical management and may be
difficult to interpret because a young infant would have maternally
acquired antibodies.
Therapy
• Supportive care is the mainstay of therapy for outpatient and
inpatient children.
• Therapeutic agents most frequently used for RSV bronchiolitis include
bronchodilators, corticosteroids, and antibiotics.
• Ribavirin (1-β-d-ribofuranosyl-1,2,4-triazole-3-carboxamide), a
synthetic nucleoside, is available for aerosol treatment for RSV
bronchiolitis among hospitalized infants.
• It is not recommended routinely, should be considered only for
infants with severe disease.
Prevention
• Prophylactic administration of humanized monoclonal antibodies
directed against the RSV F protein has been effective in reducing the
rate of RSV hospitalization.
• Multiple infection control procedures are recommended for RSV and
other agents of bronchiolitis, but among these the most effective, is
good hand hygiene.
Acute pneumonia
• It is among the top ten most common causes of death among all age
groups in the United States.
• The sixth leading cause of death in those 65 years or older, and the
single most common cause of infection-related mortality.
• The clinical challenge of treating community-acquired pneumonia is
the large number of microbial agents that can cause the disease.
Pathogenesis
• The lung is constantly exposed to the mixture of gases, particulate
material, and microbes that constitute inspired air.
• Organisms from oral secretions frequently seep down from the upper
airways as a consequence of microaspiration.
• The lower airways usually remain sterile because of the defense
mechanisms of the respiratory tract.
• The development of acute pulmonary infection indicates either a
defect in host defenses, exposure to a particularly virulent
microorganism, or an overwhelming inoculum.
• Infectious agents gain entry to the LRT through aspiration of upper
airway resident flora, inhalation of aerosolized material, and
metastatic seeding of the lung from blood.
• The defense system involves both innate and adaptive immunity.
• Mechanical clearance of entrapped organisms occurs through the
nasopharynx via expulsion or swallowing.
• In the oropharynx, the flow of saliva, sloughing of epithelial cells,
local production of complement, and bacterial interference from
resident flora serve as important factors in local host defense.
• Adherence of microorganisms to epithelial surfaces of the upper
airways is a critical initial step in colonization and subsequent
infection.
• Changes in fibronectin secretion and in binding Xteristics of
epithelium for various lectins occur as a response to underlying
diseases.
• Particles larger than 10 µm are efficiently filtered by the hair in the
anterior nares.
• The cough and epiglottic reflexes also keep large particulate matter
from reaching the central airways.
• Antigens inhaled into the alveolus and captured by APCs subsequently
activate intra-alveolar lymphoid cells.
• These cells can stimulate the migration of memory lymphocytes into
the area, leading to a localized accumulation of antigen-specific T and
B lymphocytes.
Lymphocytes in the lung have three major roles:
• antibody production
• cytotoxic activity
• inflammatory mediator production.
The lung contains a variety of cytotoxic T cells including natural killer
cells, antibody-dependent cytotoxic cells, and antigen-restricted
cytotoxic cells.
Pulmonary T cells produce a large number of cytokines.
• Mouse models suggest that unstimulated T cells produce mainly IL-2.
• After stimulation and conversion to memory T cells, two distinct groupings of
cytokines are produced.
• Th1 cells produce interferon-γ, IL-2, IL-6, and IL-10 and contribute to cell-
mediated immunity.
• Th2 cells produce IL-4, IL-5, and IL-10 and contribute to humoral immune
function.
• Furthermore, IL-3, TNF-α, granulocytemacrophage colony-stimulating factor, and
chemokines are secreted by both Th1 and Th2 phenotypes.
• Th1 cells are involved in cell mediated inflammatory reactions, whereas Th2 cells
stimulate antibody production, especially IgE, and stimulate eosinophil activity.
Examination of Sputum and
other respiratory tract samples
• Microscopic examination and culture of expectorated sputum remain
the mainstays of the laboratory evaluation of pneumonia.
• 40% to 60% of the patients will not be able to produce sputum. Of
those that do, 45% to 50% of samples may be judged to be
inadequate for further study because of oropharyngeal
contamination.
• Many patients have received antibiotics before the studies are carried
out, which drastically reduces the diagnostic yield.
• A variety of organisms cannot be detected by Gram stain, including
species of Legionella, Mycoplasma, Chlamydia, and Chlamydophila.
• However, in patients who produce sputum of adequate, diagnostic
yields of 80% for sputum Gram stain have been reported in patients
with bacteremic S. pneumoniae pneumonia.
• Despite its pitfalls, sputum Gram stain is noninvasive, can be carried
out at no risk to the patient.
• Examination of the sputum should include observation of the color, amount,
consistency, and odor.
• Mucopurulent sputum is most commonly found with bacterial pneumonia or
bronchitis.
• Scant or watery sputum is more often noted with atypical pneumonias.
• “Rusty” sputum suggests alveolar involvement and has been most commonly
associated with pneumococcal pneumonia.
• Dark red, mucoid sputum suggests Friedländer’s pneumonia caused by
encapsulated Klebsiella pneumoniae.
• Foul-smelling sputum is associated with mixed anaerobic infections most
commonly seen with aspiration.
• Sputum cultures positive for pneumococci are found in only 50% to
60% of patients with pneumonia and pneumococcal bacteremia.
• In some centers, sputum examination has been a useful means of
diagnosing Pneumocystis pneumonia in patients with AIDS.
• The use of commercially available monoclonal antibodies or Giemsa’s,
Gomori’s methenamine silver, or toluidine blue O stain has led to a
diagnosis in up to 50% of cases, making more aggressive diagnostic
procedures unnecessary.
• Special sputum staining techniques are important in identifying other
organisms such as mycobacteria
• Antigen detection in respiratory secretions has been used especially
for infections caused by S. pneumoniae, Pneumocystis, Legionella
pneumophila, and respiratory viruses.
• The direct fluorescent antibody assays for L. pneumophila and
Pneumocystis jirovecii are the most commonly used, with sensitivities
of 25% to 75% for Legionella and 80% for Pneumocystis.
• Although direct fluorescent antibody tests have been used to detect
Chlamydia trachomatis, the assay is insufficiently sensitive (varying
between 20% and 60%) for detection of Chlamydophila pneumoniae
• Nucleic acid amplification assays, especially PCR have the capability
of detecting minute amounts of material from potential pathogens,
do not appear to be influenced by prior antibiotic therapy, and can be
performed quickly.
• Although a variety of PCR techniques have been described, FDA
licensed assays exist for only M. tuberculosis and Legionella species.
Examination of pleural effusions
• Pleural effusion or parapneumonic effusion will occur in 20% to 40%
of hospitalized patients with pneumonia.
• The incidence of pleural effusions associated with pneumonia varies
with the etiologic agent, from approximately 40% to 57% with
pneumococci, to 50% to 70% with gram-negative bacilli, to up to 95%
with group A streptococci.
• Pleural fluid cultures, when positive, are specific for the organism
causing the underlying pneumonia.
• If neutrophils are not the predominant cell type seen in the pleural
space, a diagnosis other than bacterial pneumonia should be sought.
• Parapneumonic effusions can be divided into three stages.
• The first stage or exudative stage is culture negative, has a pH greater
than 7.2, glucose level greater than 60 mg/dL, and an LDH level that is
less than three times normal.
• This stage is due to pulmonary interstitial fluid entering the pleural
space and increased permeability of the capillaries in the pleura..
• Without appropriate therapy, pleural effusions become infected and
develop into the second stage or fibropurulent stage.
• This is associated with positive microbial cultures, pH less than 7.2,
glucose level less than 60 mg/dL, and LDH greater than three times
normal.
• If left untreated, fibropurulent pleural effusions will develop into stage
three effusions where a thick pleural rind is formed, restricting normal
lung expansion
• Empyema is defined as pus in the pleural space and represents a late
manifestation of complicated pleural effusions.
• PCR technology has been useful in detecting M. tuberculosis in
effusions with a sensitivity of approximately 70% and specificity of
100%.
BLOOD CULTURE
• Blood cultures are positive in 4 to 18 of patients hospitalized with
community-acquired pneumonia.
• The presence of positive blood cultures is highly specific, may be
helpful in narrowing antibiotic use.
• Blood cultures should be obtained in all patients suspected of having
bacterial pneumonia who are ill enough to be hospitalized.
• Blood cultures may be of help in patients not responding to antibiotic
therapy.
SEROLOGIC STUDIES
• Serologic assays have been used for decades to try to identify
potential etiologies of pneumonia.
• Serum antibody assays for diagnosis of M. pneumoniae and
C. pneumoniae infection have been widely used.
• The CDC and LCDC have established diagnostic standards.
Microimmunofluorescence (MIF) for serum chlamydophilal antigens
has been recommended, though enzyme immunoassays are also
available and may be more sensitive and specific.
• A variety of cytokines are released into the circulation as a result of
infection.
• Evidence suggests that these biomarkers may be useful adjuncts in
diagnosing pneumonia and predicting severity of disease.
• Procalcitonin, C-reactive protein (CRP), and soluble triggering
receptor expressed on myeloid cells (STREP-1), have been the markers
most often associated with pneumonia.
• Procalcitonin appears to be the earliest marker to appear during the
course of infection.
URINE STUDIES
• Antigen detection in urine rather than blood or sputum has become a
successful means of detecting some important pulmonary pathogens.
• Soluble L. pneumophila antigen can be detected in urine using a
commercially available enzyme immunoassay (EIA).
• Although it is useful for detecting only L. pneumophila serogroup 1,
this assay offers the advantage of being rapid and noninvasive, and it
has a sensitivity of 80% to 95% and a specificity estimated to be 99%.
• A relative problem with this method is that antigenuria may persist
for weeks to months after therapy.1
Pneumonia Prevention
• Vaccination against influenza and perhaps S. pneumoniae are
important interventions in preventing pneumonia.
• In older adults, influenza vaccine may decrease the incidence of
pneumonia by 53%.
• Influenza vaccine is suggested for any person 6 months of age or older
• The role of pneumococcal polysaccharide vaccine continues to
controversial. The incidence of bacteremia may be reduced, but the
incidence of pneumonia appears unchanged.
• Pneumococcal vaccine is recommended for patients older than 65 and
those who have recovered from community-acquired pneumonia.