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ACCP Board Review 2009 Unusual Lung Inferctions Bronchiectasis and Cystic Fibrosis

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Title: ACCP Board Review 2009 Unusual Lung Inferctions Bronchiectasis and Cystic Fibrosis


1
ACCPBoard Review 2009Unusual Lung
InferctionsBronchiectasis and Cystic Fibrosis
  • Sidney S. Braman MD FCCP
  • Providence, RI

2
Question 1 34 year old man has a non-resolving
pulmonary infiltrate. A transbronchial biopsy
shows non- filamentous branching weakly acid-fast
positive organisms consistent with nocardia lung
infection. Which statement is correct?
  • a. Culture of nocardia will take several weeks
    and will require special media
  • b The patient likely has underlying immune
    compromise
  • b. Penicillin is the treatment of choice
  • c. Clinical improvement is usually in 7-10 days
    and antibiotics should be given for 2-4 weeks

3
Question 1 34 year old man has a non-resolving
pulmonary infiltrate. A transbronchial biopsy
shows non- filamentous branching weakly acid-fast
positive organisms consistent with nocardia lung
infection. Which statement is correct?
  • a. Culture of nocardia will take several weeks
    and will require special media
  • b The patient likely has underlying immune
    compromise
  • b. Penicillin is the treatment of choice
  • c. Clinical improvement is usually in 7-10 days
    and antibiotics should be given for 2-4 weeks

4
NocardiosisEpidemiology
  • Nocardia spp. are ubiquitous soil organisms N.
    asteroides most common
  • Aerosol route most common source of infection
    lung most common clinical site
  • Rarely a laboratory contaminant
  • Infection seen with deficient cell-mediated
    immunity but can be seen with normals
  • Occurs in HIV disease when CD4lt250µL
  • Can be associated with pulmonary alveolar
    proteinosis, sarcoid and TB

5
NocardiosisDiagnosis
  • Gram positive beaded branching Gram positive
    filaments (like Actinomyces)
  • Acid fast staining weakly positive
  • Nocardia not fastidious and can grow aerobically
    on routine media in 48 hours May take 4-6 weeks
  • Blood tests not helpful

6
NocardiosisDiagnosis
  • Chest radiograph non-specific
  • pneumonia /- cavitation
  • pulmonary nodules
  • Pleural effusion and empyema
  • reticulonodular infiltrate
  • pulmonary abscess
  • Hematogenous dissemination common
  • 33 metastatic spread to brain (abscess)
  • May be asymptomatic

7
Figure 2                                        
                                                  
                                                  
                                                  
                                                  
                                                  
                                                  
                                                  
                                                  
                                                  
                                          
2 Chest Radiographs of Nocardiosis
Yildiz et al Curr Opin Pulm Med 2006
8
Treatment Nocardiosis
  • No prospective trials
  • Sulfonamides standard therapy
  • Trimethoprim/sulfamethoxazole PO or IV
  • Alternative agents minocycline, amikasin,
    imipenem, 3rd generation cephalosporins
  • Improvement 710 days, BUT treatment 6 months
    immunocompetant and 1 year for immunocompromised
    and CNS patients

9
Question 2 Which of the following is correct
aboutPulmonary Actinomycosis ?
  • a.CNS involvement is common
  • b.Organisms are weakly acid-fast
  • c.The organism can be found in the sputum on
    routine culture
  • d.The infection is treated with Penicillin

10
Question 2 Which of the following is correct
aboutPulmonary Actinomycosis ?
  • a.CNS involvement is common
  • b.Organisms are weakly acid-fast
  • c.The organism can be found in the sputum on
    routine culture
  • d. The organism is treated with Penicillin

11
PulmonaryActinomycosis
Gram-stain
  • Anaerobic gram-positive
  • Forms filaments
  • Commensals in oropharynx
  • Also GI tractfemale genitalia
  • Mainly Actinomyces israeli
  • NOT acid-fast
  • Sulfur granules are organisms
  • with amorphous center and
  • rosette of clubbed filaments

Sulfur granules
12
PulmonaryActinomycosis
  • Indolent slowly progressive course
  • Chest pain, fever, weight loss
  • No specific radiographic changes pneumonia often
    extends to the chest wall
  • Mistaken for lung cancer
  • Risk factors
  • Poor dental hygiene
  • Alcoholism
  • COPD, bronchiectasis

13
PulmonaryActinomycosis
  • The organism is not found on sputum or
    bronchoscopy not cultured anaerobically
  • Needle aspiration, transbronchial biopsy or open
    biopsy needed for diagnosis
  • No serologic tests available
  • Treatment successful (90) with penicillin or
    anaerobic coverage for 6-12 months
  • Surgical resection/drainage often needed

14
DifferencesActinomycosis vs. Nocardia
Actinomycosis
Nocardia
15
Question 3 A 21 year old man with fever and
hemoptysis
Admission Chest CT
  • 3 days prior to admission seen for sore throat
    discharged with diagnosis of viral pharyngitis
  • Epstein-Barr virus monospot test negative
  • Past history of asthma no illicit drug use
  • Presents with fever of 40C and a WBC of 27,000
  • Blood cultures positive for
  • Fusobacteruim necrphorum

16
Question 3 A 21 year old man with fever and
hemoptysis Which is the next diagnostic test to
perform?
  • a. Echocardiogram
  • b. CT scan of the abdomen
  • c. Head CT
  • d. CT scan of neck

17
Question 3 A 21 year old man with fever and
hemoptysisWhich is the next diagnostic test to
perform?
  • a. Echocardiogram
  • b. Abdominal CT scan
  • c. Head CT
  • d. CT scan of neck
  • with IV contrast
  • enhancement

Filling Defect Left Internal Jugular Vein
18
Diagnosis Lemierre Syndrome
  • Infection of lateral pharyngeal space of the neck
  • May result in septic thrombophlebitis
  • Septic pulmonary emboli may occur
  • Pharyngeal infection by anaerobic Gram- negative
    bacterium F. necrophorum, or other anaerobes
  • Must search for septic thrombophlebitis of the
    internal jugular veins
  • Infectious complications outside lung less common
    (septic arthritis, CNS)

19
Diagnosis Lemierre Syndrome
Pleural effusions and empyema common
20
Question 440 year man presents with a 2 day
history of increased cough and purulent sputum
production. He has noted some blood streaks in
his sputum. He has a history of recurrent
attacks fo bronchitis over the last several
years. His past medical history is positive for
rheumatoid arthritis. He has received
methotrexate over the last 10 months with
excellent response of his joint inflammation. He
has a 10 pack year history of smoking and stopped
smoking 10 years ago. Sputum culture is positive
for Pseudomonas aeruginosa.
21
Chest CT Scan 40 year old man with rheumatoid
arthritis
22
Question 440 year old man with rheumatoid
arthritisChoose the correct statement
  • Methotrexate should be discontinued as it has
    caused his pulmonary disease
  • Screening for cystic fibrosis is necessary given
    his positive sputum culture for Pseudomonas
    aeruginosa
  • Inhaled beta agonist therapy may be useful as it
    has been shown to reduce Pseudomonas bacterial
    adherence
  • Inhaled tobramycin is the treatment of choice for
    his new symptoms of cough and hemoptysis

23
Question 440 year old man with rheumatoid
arthritisChoose the correct statement
  • Methotrexate should be discontinued as it has
    caused his pulmonary disease
  • Screening for cystic fibrosis is necessary given
    his positive sputum culture for Pseudomonas
    aeruginosa
  • Inhaled beta agonist therapy may be useful as it
    has been shown to reduce Pseudomonas bacterial
    adherence
  • Inhaled tobramycin is the treatment of choice for
    his new symptoms of cough and hemoptysis

24
Pathophysiology of Bronchiectasis
  • External insult(infectious or toxic)

Impairedimmunesystem
Bronchial wallinflammationand destruction
Chronic orrecurrentinfection
Ciliary dyskinesiaor alteredbronchial dynamics
Ineffectivemucus clearance
Geneticpredisposition
Source http//medlib.med.utah.edu/WebPath/LUNG
25
Bronchiectasis Symptoms
  • Symptoms
  • Chronic cough
  • Dyspnea
  • Mucopurulent sputum production
  • Hemoptysis
  • Exacerbation of symptoms and antibiotic therapy 2
    or more times a year for respiratory tract
    infection

26
Chest Radiograph- typical findings
  • Chest radiograph may demonstrate parallel line
    shadows (tram-lines) (arrows), ring shadows,
    infiltrates, hyperexpansion (note flattened
    diaphragm).

27
Radiological Classification of Bronchiectasis
Cylindrical Most common
Varicose Focal Constrictions
Saccular (Cystic) Most severe
Images from Primack S, 2003.
28
Typical CT findings
  • -Tram lines horizontal course of bronchi and
    artery (See red circle)
  • -Signet-ring sign cross-section of dilated
    bronchi diametergt1.5X adjacent pulmonary artery
  • -Tree-bud pattern Bronchiolar mucus
    impaction

29
BronchiectasisPredisposing Conditions
  • Focal Disease
  • Postinfection
  • Bacterial
  • Viral
  • Mycobacterial (NTM, TB)
  • Airway obstruction
  • Foreign body
  • Bronchial stricture ( right-middle-lobe syndrome)
  • Endobronchial mass

30
BronchiectasisPredisposing Conditions
Diffuse Disease
  • Post-infection
  • Measles, pertussis
  • Mycobacterial (NTM, TB)
  • Congenital syndromes
  • Cystic fibrosis
  • Primary ciliary dyskinesia
  • Immunodeficiency states
  • Immunoglobulin deficiency
  • HIV/AIDS
  • Immune-mediated diseases
  • ABPA
  • Rheumatoid arthritis
  • Sjögrens syndrome
  • Inflammatory bowel disease
  • GERD/Aspiration

.
31
Bronchiectasis PathogensUnited Kingdom versus
United States
PatientsUK PatientsUS
N 150 () N 123 ()
Organism Haemophilus influenzae 52 (35)
37 (30.1) P aeruginosa 46 (31)
38 (30.9) Moraxella catarrhalis 30
(20) 3 (2.4) Staphylococcus aureus
21 (14) 9 (7.3) Streptococcus
pneumoniae 20 (13) 13
(10.6) Mycobacteria NA 28
(22.8) Other 27 (18) 58
(47.2) No organism isolated 34 (23)
NA
1. Pasteur MC et al. Am J Respir Crit Care Med.
20001621277-1284. 2. Nicotra MB et al. Chest.
1995108955-961.
32
Respiratory Mucosal Cytoprotection
  • Salmeterol reduces mucosal damage and number of
    adherent bacteria induced by
  • Pseudomonas aeruginosa
  • Haemophilus influenzae

Dowling RB et al. Am J Respir Crit Care Med.
1997 Dowling RB et al. Eur Respir J. 1998
33
Respiratory Mucosal CytoprotectionEffect of
Salmeterol on Pseudomonas aeruninosa infection of
respiratory mucosa
Control
Salmeterol
Dowling RB et al. Am J Respir Crit Care Med. 1997
34
Antibiotic Therapy Acute Exacerbations
  • Obtain sputum culture, review patient history of
    antibiotic use and microbial sensitivity pattern
  • Determine route of administration,
    ?hospitalization
  • Empiric coverage for potential pathogens
  • Fluoroquinolones
  • Beta-lactam agents
  • Cephalosporins, third-generation
  • Carbapenems
  • Extended spectrum penicillin
  • Imipenem
  • Aminoglycosides

Tsang KW et al. Eur Respir J. 1999141206-1209.
35
Inhaled Tobramycin Plus Ciprofloxacin (14 days)
for Acute Exacerbation of Bronchiectasis
80
PO cipro TIS
PO cipro placebo
70
60
50
Microbiologic response better Side effects
(wheeze) in 50
of Patients
40
30
20
10
0
Cured
Failed
Indeterminate
Bilton D et al. Chest 20061301503-10.
36
Maintenance Antibiotics and Other Therapies
  • Rotating antibiotics (?)
  • Aerosolized antibiotics
  • Tobramycin inhalation solution
  • Gentamicin
  • Colistin
  • Other maintenance measures
  • Anti-inflammatory agents
  • Inhaled corticosteroids
  • Chronic low-dose macrolide therapy
  • Airway clearance measures

Tsang KW et al. Eur Respir J. 199913361-364.
Anwar GA Respir Med. 20081021494-6
37
Maintenance Therapy Tobramycin Inhalation
Solution (TIS)
  • Open-label, uncontrolled study of 41 patients
    with severe bronchiectasis and P aeruginosa
  • 41 patients
  • 300 mg/5 mL TIS bid
  • 3 cycles of 2 weeks on/2 weeks off drug
  • Efficacy
  • Pulmonary symptom scores significantly improved
    over baseline
  • P aeruginosa eradicated from 22.2 of patients
  • A subset of patients had drug-related adverse
    events
  • Safety
  • Nine subjects, withdrew related to treatment. The
    most common adverse events were cough, wheezing,
    and dyspnea

Scheinberg P Chest. 20051271420-26.
38
Bronchopulmonary Hygiene
  • Techniques designed to enhance mucociliary
    clearance
  • Although widely used, there is a lack of
    consensus about the utility of these agents.
  • Airway hygiene techniques
  • Airway oscillation valves
  • Chest percussion and postural drainage
  • Autogenic drainage
  • Positive expiratory pressure therapy
  • High frequency chest compression
  • Pharmacologic agents
  • Bronchodilators
  • Mucolytics (deoxyribonuclease contraindicated)
  • Hyperosmolar agents (mannitol)

39
Bronchiectasis and Interventions
  • Bronchial artery embolization
  • Surgery may be an option for
  • Refractory, massive hemoptysis
  • Localized disease refractory to interventional
    techniques such as radiology and other therapies
  • Three studies have indicated that surgery can be
    accomplished with acceptable morbidity and
    morality

Fujimoto T et al. Ann Thorac Surg.
2001721711-1715. Agasthian T et al. Ann Thorac
Surg. 1996 62 976-978. Wilson JF, Decker AM.
Ann Surg. 1982195354-363.
40
Question 555 year old woman is known to have
stage IV sarcoidosis and type II diabetes. She
had stable shortness of breath until 6 months ago
when she began having increased dyspnea and
productive cough. For the last 2 months she has
had worsening cough, intermitant hemoptysis and
low grade fever. A 5 Kg. weight loss has been
noted. Her sputum has shown normal
respiratory flora on routine culture.
Bronchoscopy showed no endobronchial lesions.
Sputum was positive for Aspergillus sp.
41
2 Chest CT views of this 55 year old woman with
stage IV Sarcoidosis
42
55 year old woman with stage IV SarcoidosisWhat
is the next step in her management?
  • a. Treat with broad spectrum antibiotics and
    begin oral corticosteroids
  • b. Order a total IgE level and serum precipitins
    for aspergillus
  • c. Begin treatment with oral antifungal
    voriconizole
  • d. Obtain a tissue specimen of lung before
    beginning treatment

43
55 year old woman with stage IV SarcoidosisWhat
is the next step in her management?
  • a. Treat with broad spectrum antibiotics
  • b. Order a total IgE level and serum precipitins
    for aspergillus
  • c. Begin treatment with oral antifungal
    voriconizole
  • d. Obtain a tissue specimen of lung before
    beginning treatment

44
2 Chest CT views of this 55 year old woman with
stage IV Sarcoidosis
45
Aspergillosis
  • Numerous species of Aspergillus exist A.
    fumigatus most common (90)
  • Grows as septate dichotomous branching hyphae
    (acute angles) hundreds of spores
  • Are 2 to 3 µm in diameter can impact the terminal
    airways

46
Chronic Necrotizing Pulmonary Aspergillosis Also
known as semi-invasive aspergillosis
  • Much overlap with chronic cavitary pulmonary
    aspergillosis (CCPA). associated with thick
    walls, multiple cavities with aspergilloma, and
    surrounding parenchymal changes
  • Simple aspergillomas are encased by thin-walled
    cysts with little surrounding parenchyma disease
  • Chronic Necrotizing Pulmonary Aspergillosis
    patients
  • Middle-aged
  • Have some evidence of impairment of host defenses
  • Polymorphisms in mannose-binding lectin, SP-A,
    and toll-like receptors have been found
  • Have risk factors (diabetes mellitus connective
    tissue disorder poor nutritionpreexisting lung
    disease (COPD) or low dose corticosteroid
    therapy

47
Chronic Necrotizing Pulmonary Aspergillosis Also
known as semi-invasive aspergillosis
  • Clinical course is less dramatic and more
    indolent
  • Symptoms of fever, weight loss, cough, chronic
    sputum production, or hemoptysis
  • Symptoms usually present between 1 and 6 months
    before the diagnosis is made
  • Upper lobe infiltrates cavitation pleural
    thickening crescent sign from aspergilloma
  • Treatment oral therapy with one of the
    triazoles voriconazole the drug of choice 67
    improve

Camuset J et al Chest 2007 1311435-41
48
Allergic Bronchopulmonary Aspergillosis
  • A history of asthma
  • Immediate skin test reactivity to Aspergillus
  • Precipitating antibodies to A. fumigatus
  • Total IgE level greater than 1000 ng/mL
  • Peripheral blood eosinophilia gt500/mm(3)
  • Lung infiltrates on chest x-ray or chest CT
  • Central bronchiectasis on chest CT
  • Elevated specific serum IgE and IgG to A.
    fumigatus

49
Question 6An 19 year old boy with cystic
fibrosis presents with a 2 week history of
increasing cough and dyspnea. His cough is
productive of thick green sputum. There is no
fever or chest pain. He has received daily
pancreatic enzyme replacement, multivitamins, as
needed beta agonist therapy and prophylactic
cephalexin for positive sputum cultures for
Staphylococcus aureus, sensitive to
cephalosporins. The patient appears ill with an
increased respiratory rate but no fever. Chest
exam shows diffuse coarse inspiratory crackles
and ronchi over both lung fields. Sputum culture
shows a mucoid strain of Pseudomonas and Candida
spp.
50
An 19 year old boy with cystic fibrosisChose the
most correct statement
  • Intravenous anti-pseudomonal antibiotic coverage
    should begin immediately to eliminate the
    pseudomonas in his lungs
  • Antifungal therapy should be added as the patient
    shows Candida spp. in the sputum
  • His previous treatment with cephalexin likely
    caused his colonization with Pseudomonas
  • The presence of Burkholderia cepacia, also found
    in his sputum is likely a contaminant

51
An 19 year old boy with cystic fibrosisChose the
most correct statement
  • Intravenous anti-pseudomonal antibiotic coverage
    should begin immediately to eliminate the
    pseudomonas in his sputum
  • Antifungal therapy should be added as the patient
    shows Candida spp. in the sputum
  • His previous treatment with cephalexin likely
    caused his colonization with Pseudomonas
  • The presence of Burkholderia cepacia, also found
    in his sputum is likely a contaminant

52

Age-specific Prevalence of Airway
Infections Cystic Fibrosis
Cystic Fibrosis Foundation Patient Registry. 2001
53
Airway Infections in Cystic Fibrosis
  • Staphylococcus aureus is usually the first
    organism to infect young people with cystic
    fibrosis
  • Haemophilus influenzae more common at younger age
    and uncommon in young adults
  • Candida spp are the most frequent colonizers,
    isolated from 50-75 of patients with CF
    considered harmless
  • Aspergillus spp. isolated from gt25 of patients
    also not treated unless it causes allergic
    pulmonary aspergillosis
  • Nontuberculous mycobacteria (M. avium complex and
    M.abscessus) increasingly reported may need
    treatment

54
Pseudomonas Infections in Cystic Fibrosis
  • When 1st found, isolates appear normal later are
    more resistant to antibiotics and are mucoid
    strains (production of alginate)
  • Prevalence increases to gt70 in adults chronic
    antibiotics encourage colonization
  • Once established impossible to eradicate as they
    form biofilms (aggregates of bacteria)
  • For exacerbation usually aminoglycoside and ß
    lactam for synergy

55
Burkholderia cepacia complexin Cystic Fibrosis
  • Associated with accelerated decline in FEV1
  • Associated with shortened survival
  • High level of antibiotic resistance
  • No single antibiotic is effective
  • Passed from one cystic fibrosis patient to another

56
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