Ira Finegold, MD Chief of Allergy, St Luke’s-Roosevelt Hospital Center, NYC Clinical Professor...

Ira Finegold, MDChief of Allergy, St Luke’s-Roosevelt Hospital Center, NYCClinical Professor Medicine, College of Physicians and Surgeons, Columbia University, New YorkPast President ACAAI

Ira Finegold,MD

Learning Objectives:

1. To review the many causes of persistent cough.

2. To Become aware of the role non tuberculous mycobacteria may play in patients with prolonged coughs

Cough : Common Causes Smoking and other environmental irritants Postnasal drip Asthma Gastroesophageal reflux Chronic bronchitis Transient airway hyperresponsiveness

(e.g., after viral upper respiratory infection)

Medication-related (ACE inhibitors, beta blockers

Cough: Uncommon causes Congestive Heart Failure Cancer (bronchogenic or esophageal) Interstitial lung disease (emphysema

or sarcoidosis) Bronchiectasis Tuberculosis and other chronic lung

infections (e.g., fungal) Cystic fibrosis Recurrent aspiration (e.g., post-

stroke, frequent vomiting [bulimia], alcoholism)

Cough: Uncommon causes Pressure from an intrathoracic mass (e.g.,

thoracic aneurysm, thyromegaly, mediastinal lymphadenopathy)

Irritation of cough receptors in ear (e.g., impacted cerumen, hair, foreign body)

Opportunistic infections in immunosuppressed patients

Lymphangitis carciomatosis Foreign body Chronic inhalation of bronchial irritants

(occupational) Psychogenic

EG

DOB: 1939 WF Executive History of pollen allergy and frequent

infections in childhood Bronchiectasis, and positive NTM

1999.

EG

Symptoms: Cough, Dyspnea, Night sweats, weight loss and fatigue. No fever

PE: Unremarkable –thin WF

EG LAB

1999: IgG said to be normal 2/14/05 IgG 686 8/11/06 IgG 765 7/10/2007 IgG 820 IgG2 decr. Sputum cultures:

Many positive for m.avium, m. abcessus

EG LAB

CT SCAN 5/07 Abnormal, recently improving, brochiectasis

5/21/07 WBC : 3,770 Monocytes 12.7%

IgE : 269 multiple drug allergies

EG Meds

Tigecycline IV Clarithromycin Ethambutol Rifampin Moxifloxacin Sulfamethoxazole/trimethoprim Fluconazole, Tiotropium

NTM Morphotype

Middle aged white females Slender, tall, Scoliosis, Pectus excavatum Mitral Valve prolapse Higher percentage of CFTR genes No cellular immune defects

Iseman & Marras AJRCCM 178:999, 2008, Kim et al. 1066-1074.

Kim, et al. Pulmonary Nontuberculous Mycobacterial Disease Am J Resp Crit Care Med 178:1066, 2008



Mycobacteria are a family of small, rod-shaped bacilli.

The most recognized of the family are M. tuberculosis (TB) and M. leprae ( Hansen’s Disease or leprosy).

Unlike TB and leprosy, which are primarily spread human-to-human, the NTM are believed to be acquired from the environment - hence the alternative label, “environmental mycobacteria.”

04/18/23

What are the NTMs?

Nontuberculous Mycobacterial Lung Disease

NTM Pulmonary* PathogensNontuberculous Mycobacterial Lung Disease

Common

M. avium

M. intracellulare

M. kansasii

M. abscessus

M. chelonae (kell oh’ nye)

Infrequent

M. xenopi (zin oh’ pee)

M. szulgai (sull’ guy)

M. malmoense

(mal’ moh en suh)

M. fortuitum

*Other NTMs are very rare pulmonary pathogens but may present as extrapulmonary pathogens; see ATS guidelines

}MAC

NTM Pulmonary* PathogensNontuberculous Mycobacterial Lung Disease

Rare

M. celatum (sell ah’ tum)

M. scrofulaceum

M. simiae

M. terrae

M. immunogenum

Never (almost)

M. gordonae

*Other NTMs are very rare pulmonary pathogens but may present as extrapulmonary pathogens; see ATS guidelines

Mycobacterium avium complex lung diseaseBackground


Not reportable disease - historicallyNot reportable disease - historically 1979-80 : NTM 1/3 of all mycobact isolates1979-80 : NTM 1/3 of all mycobact isolates 1990-91 : NTM 3/4 of all mycobact isolates1990-91 : NTM 3/4 of all mycobact isolates Increased prevalence not well characterizedIncreased prevalence not well characterized Historically, case rate (MAC) estimated Historically, case rate (MAC) estimated

between 0.9 and 4.6 per 100,000 between 0.9 and 4.6 per 100,000 Ontario: ’97-’99 - Ontario: ’97-’99 - 6.36.3/100k to ’01-’03 /100k to ’01-’03

9.39.3/100k/100k( U.S. TB case rate 2004 4.9 / 100,000)( U.S. TB case rate 2004 4.9 / 100,000)

Not reportable disease - historicallyNot reportable disease - historically 1979-80 : NTM 1/3 of all mycobact isolates1979-80 : NTM 1/3 of all mycobact isolates 1990-91 : NTM 3/4 of all mycobact isolates1990-91 : NTM 3/4 of all mycobact isolates Increased prevalence not well characterizedIncreased prevalence not well characterized Historically, case rate (MAC) estimated Historically, case rate (MAC) estimated

between 0.9 and 4.6 per 100,000 between 0.9 and 4.6 per 100,000 Ontario: ’97-’99 - Ontario: ’97-’99 - 6.36.3/100k to ’01-’03 /100k to ’01-’03

9.39.3/100k/100k( U.S. TB case rate 2004 4.9 / 100,000)( U.S. TB case rate 2004 4.9 / 100,000)



Now more than 125 identified NTM species MAC (Mycobacterium avium complex) most

common Ubiquitous: soil and water Animal to human and human to human

transmission not documented Asymptomatic infections and symptomatic

disease in humans possible

Now more than 125 identified NTM species MAC (Mycobacterium avium complex) most

common Ubiquitous: soil and water Animal to human and human to human

transmission not documented Asymptomatic infections and symptomatic

disease in humans possible

Diagnosis and treatment of lung infection with nontuberculous mycobacteriaArend et al. Current Opinion in Pulmonary Medicine 2009,

NTM Infections in New Hosts

Over the past 25 years, there has been a dramatic increase in the number of NTM cases seen by pulmonary and ID clinicians across the U.S. The epidemiology has changed - now

predominantly seen in Caucasian women of middle age and older

Usually with a negative or negligible smoking history

Commonly with a slender body habitus


The New NTM ATS GuidelinesAJRCCM 175: 367-416, 2007

The New NTM ATS GuidelinesAJRCCM 175: 367-416, 2007

•Similar diagnostic criteria for MAC and NTM lung diseaseSimilar diagnostic criteria for MAC and NTM lung disease

•3 of 3 criteria required:3 of 3 criteria required:

•History and physical exam - clinical presentationHistory and physical exam - clinical presentation

•Chest radiography / Chest radiography / Chest CTChest CT

•Microbiology / histopathologyMicrobiology / histopathology

•Similar diagnostic criteria for MAC and NTM lung diseaseSimilar diagnostic criteria for MAC and NTM lung disease

•3 of 3 criteria required:3 of 3 criteria required:

•History and physical exam - clinical presentationHistory and physical exam - clinical presentation

•Chest radiography / Chest radiography / Chest CTChest CT

•Microbiology / histopathologyMicrobiology / histopathology

Mycobacterium avium complex lung diseaseClinical Presentation


Variable presentation:

• Group 1 : Preexisting lung disease

• Group 2 : No previous lung disease

• Group 3 : Hot tub lung (HTL)

• Group 4 : HIV

• Group 5 : Interleukin-12 / -IFN defects

Variable presentation:


• Group 2 : No previous lung disease

• Group 3 : Hot tub lung (HTL)

• Group 4 : HIV

• Group 5 : Interleukin-12 / -IFN defects



Markedly abnormal pulmonary function tests

Associated diseases: COPD, past granulomatous lung disease (TB, fungal), radiation fibrosis, bronchiectasis, silicosis

CF: increased recognition of MAC as well as other NTM

Markedly abnormal pulmonary function tests

Associated diseases: COPD, past granulomatous lung disease (TB, fungal), radiation fibrosis, bronchiectasis, silicosis

CF: increased recognition of MAC as well as other NTM

• Group 1 : Preexisting lung diseaseGroup 1 : Preexisting lung disease• Group 1 : Preexisting lung diseaseGroup 1 : Preexisting lung disease




Localized or diffuse fibrocavitary disease

Male predominance: smokers

Age: 6th to 8th decade


Localized or diffuse fibrocavitary disease

Male predominance: smokers

Age: 6th to 8th decade



• Group 2 : No previous lung disease (Most common)

• Group 2 : No previous lung disease (Most common)

Mild abnormal pulmonary function tests: obst, Mild abnormal pulmonary function tests: obst, restrictive, mixedrestrictive, mixed

• Associated findings: Associated findings: mitral valve prolapsemitral valve prolapse, , pectus pectus excavatumexcavatum

• Functional IFN-Functional IFN- defects not detected; increased defects not detected; increased CFTR mutations notedCFTR mutations noted

Mild abnormal pulmonary function tests: obst, Mild abnormal pulmonary function tests: obst, restrictive, mixedrestrictive, mixed

• Associated findings: Associated findings: mitral valve prolapsemitral valve prolapse, , pectus pectus excavatumexcavatum

• Functional IFN-Functional IFN- defects not detected; increased defects not detected; increased CFTR mutations notedCFTR mutations noted

Common Features of NTM Lung Disease Clinical:

Insidious onset of cough; initially dry, then variably productive of mucopurulent secretions; occasionally bloody. Cough may be precipitated by lying down.

Dyspnea Fever, chills, night sweats are not

uncommon Recurrent “bronchitis,” or “walking

pneumonia” Vague malaise and diminished energy Occasionally, focal chest discomfort


Mycobacterium avium complex lung diseaseRadiographic Findings

Mycobacterium avium complex lung diseaseRadiographic Findings

Nodular infiltrates Cavity and fibrocavitary disease with or

without thickened walls Consolidation Solitary or multiple pulmonary nodules Cylindrical, cystic, or saccular bronchiectasis___________________________________________ *Pleural disease, prominent mediastinal/hilar

adenopathy, air-fluid levels, and on high resolution chest computed tomography are not commonly associated with MAC in patients with MAC-PD associated with preexisting disease. Ground glass opacities common (HTL) may be present.

Nodular infiltrates Cavity and fibrocavitary disease with or

without thickened walls Consolidation Solitary or multiple pulmonary nodules Cylindrical, cystic, or saccular bronchiectasis___________________________________________ *Pleural disease, prominent mediastinal/hilar

adenopathy, air-fluid levels, and on high resolution chest computed tomography are not commonly associated with MAC in patients with MAC-PD associated with preexisting disease. Ground glass opacities common (HTL) may be present.

Common Features of NTM Lung Disease

Chest Radiography: Chest X-rays typically reveal amorphous,

lower zone shadowing Upper lobe cavitary disease (like TB) is

uncommon; however, cavities may be present in other zones

High Resolution Computed Tomography (HRCT) lung scans are the primary diagnostic aid in recognizing NTM disease

HRCT scans often reveal predominantly right middle lobe and/or lingular disease


NTM Infection PresentationNontuberculous Mycobacterial Lung Disease

Common CXR findings:

A. Hazy opacity abutting the heart border [#1]

1

Common CXR findings:

B. Retrosternal shadowing overlying the cardiac silhouette [#2]


NTM Infection Presentation

2

NTM Infection Presentation


Common HRCT scan findings:A.Volume loss and variable

opacities of the right-middle lobe (RML) and lingular segment of the left-upper lobe (LING)

B. Saccular or “honeycomb” bronchiectasis in both the RML & LING

C. Diffuse cylindrical and varicoid bronchiectasis with scattered nodular opacities

[RML] [LING]

Mycobacterium avium complex lung disease: Microbiology / histopathology

Mycobacterium avium complex lung disease: Microbiology / histopathology

Sputum/wash: multiple positive cultures, smears; > 2

Single wash available w/o sputum: positive culture, independent of smear

Tissue: culture positive, granulomas w/ positive sputum/wash

Sputum/wash: multiple positive cultures, smears; > 2

Single wash available w/o sputum: positive culture, independent of smear

Tissue: culture positive, granulomas w/ positive sputum/wash

ATS: AJRCCM 175: 367, 2007ATS: AJRCCM 175: 367, 2007ATS: AJRCCM 175: 367, 2007ATS: AJRCCM 175: 367, 2007

Mycobacterium avium complex lung diseaseNatural History


Colonization?Colonization?Colonization?Colonization?

InfectionInfectionInfectionInfection

Disease Disease (treatment)(treatment)Disease Disease (treatment)(treatment)

Diagnosis = Treatment ???Diagnosis = Treatment ??? Diagnosis = Treatment ???Diagnosis = Treatment ???



• Limited data, esp. those w/o pre-existing lung disease and immunocompetent

• Slow progression (years), non-cavitary nodular with cylindrical bronchiectasis

• Culture conversion not likely to occur with bronchial hygiene alone when ‘infection’ present

• Limited data, esp. those w/o pre-existing lung disease and immunocompetent

• Slow progression (years), non-cavitary nodular with cylindrical bronchiectasis

• Culture conversion not likely to occur with bronchial hygiene alone when ‘infection’ present



• Spectrum of disease: mild symptoms to respiratory failure/death-advanced lung disease

• Clinical and microbiologic status parallel

• Relapse possible post-treatment

• Spectrum of disease: mild symptoms to respiratory failure/death-advanced lung disease

• Clinical and microbiologic status parallel

• Relapse possible post-treatment

Mycobacterium avium complex lung diseaseTreatment


• Overall sputum conversion rates 78%Overall sputum conversion rates 78%

• Previously treated conversion rates 55-64%Previously treated conversion rates 55-64%

• Naïve treatment patient conversion 74-92%Naïve treatment patient conversion 74-92%

• Non-cavitary disease 82-92%Non-cavitary disease 82-92%

• Fibrocavitary disease 74%Fibrocavitary disease 74%

• Overall sputum conversion rates 78%Overall sputum conversion rates 78%

• Previously treated conversion rates 55-64%Previously treated conversion rates 55-64%

• Naïve treatment patient conversion 74-92%Naïve treatment patient conversion 74-92%

• Non-cavitary disease 82-92%Non-cavitary disease 82-92%

• Fibrocavitary disease 74%Fibrocavitary disease 74%

Aksamit,T.R. et al. AJRCCM 161:A725,2000Aksamit,T.R. et al. AJRCCM 161:A725,2000Griffith, D.E. et al. Clin Infect Dis 30:288,2000Griffith, D.E. et al. Clin Infect Dis 30:288,2000Tanaka, E. et al. AJRCCM 160: 866, 1999Tanaka, E. et al. AJRCCM 160: 866, 1999Dautzenberg, B. et al. Chest 107: 1035,1995Dautzenberg, B. et al. Chest 107: 1035,1995

Aksamit,T.R. et al. AJRCCM 161:A725,2000Aksamit,T.R. et al. AJRCCM 161:A725,2000Griffith, D.E. et al. Clin Infect Dis 30:288,2000Griffith, D.E. et al. Clin Infect Dis 30:288,2000Tanaka, E. et al. AJRCCM 160: 866, 1999Tanaka, E. et al. AJRCCM 160: 866, 1999Dautzenberg, B. et al. Chest 107: 1035,1995Dautzenberg, B. et al. Chest 107: 1035,1995

Elements of NTM Disease Diagnosis

Clinical History (Demographics) Radiography Microbiology

A. Spontaneous sputum sample B. Induced sample (hypertonic saline nebs) C. Bronchoscopy, if A and B fail to yield

results D. Be sure to culture for other potential

bacterial and fungal pathogens


Clinical Presentations Recap:

Clinical Presentations Recap:

Chronic cough - variably productive for years Fatigue, often severe Malaise Weight loss Night sweats Feverishness

*Some of these symptoms can also be attributed to

menopause, possibly leading to a delay in diagnosis

04/18/23

Symptoms


Possible predisposing or co-existing conditions: Cystic Fibrosis, including adult-onset variants

Primary ciliary dyskinesia (immotile cilia or Kartagener’s Syndrome)

Alpha-1 antitrypsin anomalies GERD with aspiration Prior histoplasmosis or TB HIV, Immunosuppresive drugs, Anti

TNF-α


American Thoracic Society (ATS) Diagnostic Criteria Originally published in 1997; revised 2007 Critical issue: since the NTM are

widespread in the environment, a single isolation is usually NOT sufficient for diagnosis/initiation of therapy

General guidelines for the typical NTMs (MAC., M. abscessus) A) 2 or more (+) cultures B) or a (+) smear and (+) culture C) or (+) bronch wash culture

Am. J. Respir. Crit. Care Med. 175:367-416, 2007


Treating Pulmonary NTM Infection

ATS guidelines describe chemotherapy options; basic principle - analogous to TB- use multiple drugs to increase efficacy and to prevent acquired resistance.

ATS guidelines usually suggest standard regimens based on accurate identification of species, e.g. regimen “X” for M. kansasii.

Role of in vitro susceptibility (s) testing is debated consistent agreement for in vitro (s) testing

for macrolides in MAC; standard panel for rapidly-growing NTMs,

such as M. abscessus or M. chelonae;


2007 ATS Guidelines for Treatment of MAC:1. Initial Rx for nodular-bronchiectatic disease is TIW

a. Clarithromycin 1000 or azithromycin 500 mg b. Ethambutol 25 mg/kg c. Rifampin 600 mg

2. Initial RX for fibrocavitary or severe nodular- bronchiectatic disease is DAILY

a. Clarithromycin 500-1000 or azithromycin 250 mg b. Ethambutol 15 mg/kg c. Rifampin 10 mg/kg to maximum 600

3. Goal: 12 months of negative cultures while on therapy

4. Surgery may be useful in localized disease Am J Respir Crit Care Med 175:367-416, 2007



•ObservationObservation

•Medical therapyMedical therapy : Triple drug therapy : Triple drug therapyClarithromycin /azithromycin, rifampin/rifabutin , ethambutol Clarithromycin /azithromycin, rifampin/rifabutin , ethambutol +/- streptomycin/amikacin first 2-3months+/- streptomycin/amikacin first 2-3months12 month culture negativity12 month culture negativityRole of quinolones, clofazimine, others ?Role of quinolones, clofazimine, others ?

•Adjunctive therapyAdjunctive therapy::Recent negative inhaled IFN-Recent negative inhaled IFN- trial trial

•ObservationObservation

•Medical therapyMedical therapy : Triple drug therapy : Triple drug therapyClarithromycin /azithromycin, rifampin/rifabutin , ethambutol Clarithromycin /azithromycin, rifampin/rifabutin , ethambutol +/- streptomycin/amikacin first 2-3months+/- streptomycin/amikacin first 2-3months12 month culture negativity12 month culture negativityRole of quinolones, clofazimine, others ?Role of quinolones, clofazimine, others ?

•Adjunctive therapyAdjunctive therapy::Recent negative inhaled IFN-Recent negative inhaled IFN- trial trial




•SurgerySurgery

•Other contributing factors:Other contributing factors:Bronchiectasis, GERD, sinus diseaseBronchiectasis, GERD, sinus disease

•Hot Tub LungHot Tub Lung: Ag removal +/- steroids,: Ag removal +/- steroids, antimycobacterial Rxantimycobacterial Rx

•SurgerySurgery

•Other contributing factors:Other contributing factors:Bronchiectasis, GERD, sinus diseaseBronchiectasis, GERD, sinus disease

•Hot Tub LungHot Tub Lung: Ag removal +/- steroids,: Ag removal +/- steroids, antimycobacterial Rxantimycobacterial Rx


Mycobacterium avium complex lung disease AJRCCM 175: 367-416, 2007

Mycobacterium avium complex lung disease AJRCCM 175: 367-416, 2007CONTROVERSIES: Is one macrolide, clarithromycin or

azithromycin, superior to another in the treatment of MAC lung disease?

Does the inclusion of an injectable agent early in the treatment of MAC lung disease improve long-term outcome?

Is one rifamycin, rifabutin or rifampin, superior to another in the treatment of MAC lung disease?

CONTROVERSIES: Is one macrolide, clarithromycin or

azithromycin, superior to another in the treatment of MAC lung disease?

Does the inclusion of an injectable agent early in the treatment of MAC lung disease improve long-term outcome?

Is one rifamycin, rifabutin or rifampin, superior to another in the treatment of MAC lung disease?

2007 ATS Guidelines for Treatment of M. kansasii

Summary of ATS Recommendations for M. kansasii therapy

1. Daily regimen might include: a. Rifampin 10 mg/kg/day to maximum 600 mg b. Ethambutol 15 mg/kg/day c. Isoniazid 5 mg/kg/day to maximum 300 mg*

2. Goal: 12 months of negative cultures while on therapy

* Recent data suggest that macrolides (clarithromycin or azithromycin) may be substituted for INH; not part of ATS Recommendations.

Am J Respir Crit Care Med 175:367-416, 2007

2007 ATS Guidelines for Treatment of M. chelonae-abscessus

Summary of ATS Recommendations for M. abscessus* Therapy

1. The only predictably curative therapy of limited (focal) M. abscessus lung disease is surgical resection combined with multidrug chemotherapy.

2. Periodic multidrug therapy (a macrolide and 1 or more parenteral agents including amikacin, cefoxitin or imipenem or a combination of the parenteral agents) may help control symptoms and/or progression of disease.

* Management of M. chelonae disease is analogous.

Am J Respir Crit Care Med 175:367-416, 2007

Complementary Elements of Therapy

Patients with bronchiectasis often benefit from bronchial hygiene: Airway agitating devices (Acapella®, Flutter®

or Pep valves) Inhaled bronchodilating/anti-inflammatory

agents, including -agonists, anti-cholinergics and/or steroids

If patient has co-existing sinusitis (a common finding), management may improve cough

GERD, if present (also a common finding), may provoke cough and periodically soil the lungs. Acid-inhibition may not be sufficient; may need measures to prevent reflux (posture in bed, meal patterns or, rarely, surgical repair).


Management Strategies:Management Strategies:

Duration: Varies widely by patient, disease

severity and tolerance to medications Average duration is 12-24 months Rapidly growing NTM infections may

require intermittent treatment across lifetime

04/18/23



Objectives: Improved quality of life and overall

strength Significant reduction in constitutional

and radiographic symptoms Traditionally, sputum sterilization

was the goal; still important, but not sufficient

04/18/23



Surgery: Surgical resection may be an option

for localized disease. Debulking of diseased tissue may

significantly reduce symptoms and the spread of disease in some patients.

Strongly consider referral to a specialty center when considering surgery.

04/18/23


Respondent Characteristics

Gender 38 (83%) women 8 (17%) men

Race 45 (98%) White 1 Native American

Employment 20 (43%) employed 26 (57%) not

employed

Age Range: 15-80 Median: 60 years Mean (SD): 59 (11)

01

23

45

FR

EQ

UE

NC

Y

20 40 60 80

AGE

Onset and Diagnosis Age at onset of

symptoms Range: 3-78 years

old Median: 55 Mean (SD): 52 (16)

Years from symptoms to diagnosis Range: 0-30 years Median: 1 Mean (SD): 4 (6)

01

23

4

FR

EQ

UE

NC

Y

0 20 40 60 80

AGE AT ONSET OF SYMPTOMS

05

1015

FR

EQ

UE

NC

Y

0 10 20 30

YEARS FROM SYMPTOMS TO DIAGNOSIS

NTM Medication Use

Took meds for NTM 34 (74%) yes 12 (26%) no

Cycles of therapy Range: 0-20 cycles Median: 1 Mean (SD): 1 (3)

05

1015

20

0 5 10 15 20

CYCLES OF THERAPY

Condition in Last 12 Months Culture (22 responses)

13 (59%) Still positive

9 (41%) Converted to negative

X-ray (33 responses) 8 (24%) worsened 25 (76%) not

worsened

Symptoms— cough, hemoptysis,

weight loss, loss of appetite, fatigue, shortness of breath, fever, depression

(41 responses) 21 (51%) at least

one symptom worsened

20 (49%) not worsened

Consultation

Many cases of NTM Lung Disease are difficult to manage

Early consultation may be helpful: Referrals -

Informational - this site provides free informational sources: www.NTMinfo.org

Referrals - Regional specialists National referral programs:

Mayo Clinic National Jewish Medical and Research Center Stanford University University of Texas, Tyler


Who doesn’t ‘have’ NTM?

Findings may represent colonization of the lower respiratory tract

CF patients 13% positive culture Some organisms are unlikely

pathogens Eg M. gordonae

Other patients seen in one year PF 70 yo wf history of AR Chest x-ray

bronchiectasis, m.abcesses EG 67 wf Sickly child, brochiectasis m. abcessus,

m. avium, multiple drug allergies, IgE 269, IgG 686

EK 73 yo WF Rx’d for TB age 8, 18,26, Bronchiectasis, Nl IgG

MR 61 yo WF coughing for 5 years, M. avium complex

TH 46 yo WF coughing 6 years , Thyroid surgery, Calcium 7.8, IgG 660 IgG1 and 4 , IgE 14 MAC

AJ: 51 HF Health aid m. avium RM 63 yo WM α1 antitrypsin, 2 yrs previously

MAC IgE:12 RY 62 yo wm smoker COPD IgE 122, IgG 859 MAC KK 46 yo wf. Nl IgG Biopsy NTM Granulomas

Serum IgG Levels in NTM Patients

Immunopathology

Central to pathogenisis of MTB- Failure to contain organism

Defects in IL-12, IFN-γ Expression of IL-8, FOXP3 , IL-12β

can distinguish between latent and active TB *

*Wu, Huang et al. J Immunol 178:3688, 2007

Immunopathology NTM KIM AJRCCM:2008 Stimulated cytokine production was

similar to that of healthy control subjects, including the IFN-γ/IL-12 pathway. CD41, CD81, B, and natural killer cell numbers were normal.

A total of 36% of patients had mutations inthe cystic fibrosis transmembrane conductance regulator gene

Take Home Lesson

For patients with chronic productive coughs defying diagnostic maneuvers and not responding to conventional therapy,

Consider the possibility of NTM and order sputums for AFB stain and Culture and sensitivity

Questions and Thank you!

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Ira Finegold, MD Chief of Allergy, St Luke’s-Roosevelt Hospital Center, NYC Clinical Professor...

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