Your SlideShare is downloading. ×
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Chronic respiratory disease, ics and risk of ntm2
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×
Saving this for later? Get the SlideShare app to save on your phone or tablet. Read anywhere, anytime – even offline.
Text the download link to your phone
Standard text messaging rates apply

Chronic respiratory disease, ics and risk of ntm2

289

Published on

Published in: Health & Medicine
0 Comments
2 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total Views
289
On Slideshare
0
From Embeds
0
Number of Embeds
1
Actions
Shares
0
Downloads
0
Comments
0
Likes
2
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide

Transcript

  • 1. Chronic Respiratory Disease, Inhaled Corticosteroids and Risk of Non-tuberculous Mycobacteriosis (NTM) 臨藥科技所 碩一 陳秋縈 指導老師 張慧真主任 Feb 6th, 2013
  • 2.  Background  Chronic respiratory disease and ICS therapy for COPD increase the risk of pneumonia. Limited data on NTM.  Objective  Examine different type of chronic respiratory disease and ICS therapy as risk factors for NTM pulmonary disease  Study design  Population-based case-control study  Study population  All adults in Denmark with microbiologically confirmed NTM pulmonary disease between 1997 and 2008 ICS: inhaled corticosteroids NTM: Nontuberculous Mycobacteria Chronic respiratory disease, inhaled corticosteroids and risk of non-tuberculous mycobacteriosis (NTM) Thorax. 2012 Jul 10. ORIGINAL ARTICAL 2
  • 3. Results  Risk is increased in patient with chronic respiratory disease  OR for NTM pulmonary disease Any chronic respiratory disease 16.5 (95% CI 12.2 to 22.2) − Bronchiectasis 187.5 (95% CI 24.8 to 1417.4) − Tuberculosis history 178.3 (95% CI 55.4 to 574.3) − COPD 15.7 (95% CI 11.4 to 21.5) − Pneumoconiosis 9.8 (95% CI 2.03 to 52.8) − Asthma 7.8 (95% CI 5.2 to 11.6)  Among COPD patients, risk is associated with use, dose and type of ICS  OR for NTM pulmonary disease regard to COPD and ICS use − Use: concurrent ICS vs. never received ICS 29.1 vs. 7.6 − Dose: low-dose ICS vs. high-dose ICS 28.1 vs. 47.5 − Type: OR was higher for fluticasone than for budesonide 31.0 vs. 19.8  Conclusion  Chronic respiratory disease, particularly COPD treated with ICS therapy, is a strong risk factor for NTM pulmonary disease. 3
  • 4. Inhaled Corticosteroids (ICS) and risk of pulmonary infection in COPD 4
  • 5. ICS Increase Risk of Pulmonary Infection in COPD Possible mechanism  ICS  Achieve locally high concentrations in the lung which may lead to local immunosuppressive effects  COPD  Persistent inflammation causing airway and mucosal damage  Compromising local immunity  Impaired clearance of secretions  Susceptible patient to high risk of colonization with pathogenic 5
  • 6.  Increased risk of pneumonia associated with3  Any inhaled corticosteroid (RR 1.57, 95% CI 1.41-1.75, NNH 33-60)  Fluticasone (RR 1.67, 95% CI 1.47-1.89, NNH 28-53)  For budesonide  No significant association with increased risk of pneumonia2,3  Budesonide/Formoterol reported to have lower risk of pneumonia than Fluticasone/Salmeterol in patients with COPD 1  Increased risk of pneumonia is not accompanied by a corresponding increase in mortality3,4 1. Int J Clin Pract 2011 Jul;65(7):764 2. Lancet 2009 Aug 29;374(9691):712 3. Curr Opin Pulm Med 2010 Mar;16(2):118 4. Arch Intern Med 2009 Feb 9;169(3):219 ICS Increased Risk of Pneumonia in COPD Literature review 6
  • 7. Risk of Pneumonia Between Different Types of ICS Possible mechanism  Potency and dosage  Effect of delivery devices − Primary determinants of the dose delivered to the lungs − ex. Lung delivery of metered-dose inhaler (MDI): 20 %  Pulmonary retention time  Removed from the lungs before it substantially downregulates local immunity and allows proliferation of bacteria Proc Am Thorac Soc. 2004;1(4):356-63. Ann Pharmacother. 2009 Mar;43(3):519-27 7
  • 8. Potency and Estimated Comparative Daily Dosages for ICS Comparative daily dose (mcg) Drug Recepter binding affinity Low Medium High Beclomethasone MDI 0.4/13.5 80 -240 240 -480 >480 Budesonide DPI 9.4 200 -600 600 -1200 >1200 Ciclesonide MDI 0.12/12.0 80 -320 320 -640 >640 Flunisolide MDI 1.8 320 320 -640 >640 Fluticasone MDI DPI 18 88 -264 100 -300 264 -440 300 -500 >440 >500 Mometasone DPI 23 220 440 >440 Adapted from National Asthma Education and Prevention Program: Expert Panel Report III: Guidelines for the diagnosis and management of asthma. Bethesda, MD. National Heart, Lung, and Blood Institute, 2007. (NIH publication no. 08-4051) www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm (Accessed on December 6, 2012).  Potency depends on their receptor-binding affinity  Potency is the major determinants of the relative comparable doses 8
  • 9. Risk of Pneumonia Between Different Types of ICS Possible mechanism  Potency and dosage  Effect of delivery devices − Primary determinants of the dose delivered to the lungs − ex. Lung delivery of metered-dose inhaler (MDI): 20 %  Pulmonary retention time  Removed from the lungs before it substantially downregulates local immunity and allows proliferation of bacteria Proc Am Thorac Soc. 2004;1(4):356-63. Ann Pharmacother. 2009 Mar;43(3):519-27 9
  • 10. Comparison of Delivery Devices Device Advantages Disadvantages MDI Slow deep inhalation • Portable • Convenient • Nonbreath-activated • Patient coordination essential • High pharyngeal deposition • Difficult to deliver high doses DPI Rapid deep inhalation • Portable • Convenient • Breath-activated • Propellant not required • Difficult to deliver high doses • High pharyngeal deposition • Cannot use with endotracheal or tracheostomy tubes Nebulizer • Patient coordination not required • High doses possible • Expensive • Contamination possible • Device preparation required MDI: Metered-dose inhaler DPI: Dry powder inhaler Terbuhaler Accuhaler Evohaler 10
  • 11. Risk of Pneumonia Between Different Types of ICS Possible mechanism  Potency and dosage  Effect of delivery devices − Primary determinants of the dose delivered to the lungs − ex. Lung delivery of metered-dose inhaler (MDI): 20 %  Pulmonary retention time  Removed from the lungs before it substantially downregulates local immunity and allows proliferation of bacteria Proc Am Thorac Soc. 2004;1(4):356-63. Ann Pharmacother. 2009 Mar;43(3):519-27 11
  • 12. Pharmacodynamic/Pharmacokinetic Properties of ICS Ann Pharmacother. 2009 Mar;43(3):519-27. Proc Am Thorac Soc. 2004;1(4):356-63.  Retention of ICS in the lung  Lipophilicity, Lipid Conjugation  Distribution into the lipophilic tissues of the lung and slow absorption into the systemic circulation Fluticasone is 6 to 8 times more lipophilic than budesonide. Budesonide is more rapidly cleared from airways than fluticasone. 12
  • 13. 本院吸入性類固醇品項 Drug Device Dose per container Indication Dosage Cost /bot Budesonide (Pulmicort Turbuhaler) 200mcg/dose DPI 100 doses/btl Asthma Adult: 200-400 mcg bid Child: 50-200 mcg bid 366 Budesonide (Duasma) 200mcg/puff MDI 200 puffs/btl Asthma Adult: 200-400 mcg bid Child 6-12 yr: 100-200 mcg bid 394 Budesonide (Pulmicort Respule) 1mg/2ml/amp Nebulizer Once Asthma Adult: 0.5-1 mg bid Child 6-12 yr: 0.25-0.5 mg bid 67 Fluticasone (Flixotide Accuhaler) 250mcg/dose DPI 60dose/btl Asthma Adult: 100-1000 mcg bid 250mcg 不適用於兒童 Children: 50-100 mcg bid 545 Salmeterol + Fluticasone (Seretide Evohaler) 25/50mcg/dose 25/250mcg/dose MDI 120dose/btl Asthma COPD Adult and child≧4 yr: 2puff bid Adult and child≧12 yr: 2puff bid 819 1433 Salmeterol + Fluticasone (Seretide Accuhaler) 50/250mcg/dose DPI 60 doses/btl Asthma COPD Adult and child≧ 4 yr: 1 puff bid 1060 Formoterol + Budesonide (Symbicort Turbuhaler) 4.5/160mcg/dose DPI 120dose/btl Asthma COPD Adults & children > 12 yrs, 1-2 doses bid 1257 Beclomethasone + Formoterol (Foster) 100/6mcg/dose MDI 120dose/btl Asthma Adult≧18yr: 1-2 puff bid 需冷藏,拆封後室溫保存可達 5個月 992 13
  • 14. Nontuberculous Mycobacteria (NTM)  Introduction  Epidemiology  Diagnostic criteria  Treatment 14
  • 15. Nontuberculous Mycobacteria (NTM)  Mycobacteria other than M. Tuberculosis and M. Leprae  More than 140 NTM species identified  One third have been associated with disease in humans  Environmental organisms found in water and soil  Not contagious: no evidence of human-to-human transmission Am J Respir Crit Care Med. 2007;175:367–416. Uptodate 15
  • 16. Classification of NTM  Rapidly growing mycobacteria (RGM)  M. abscessus, M. chelonae, M. fortuitum  Slowly growing mycobacteria (SGM)  Photochromogens − M. kansasii, M. Marinum, M. Simiae, M. asiaticum  Scotochromogens − M. scrofulaceum, M. xenopi, M. szulgai, M. flavscens, M. gordonae  Nonchromogens − M. avium complex (MAC), M. Malmoense, M. Ulcerans, M. Terrae complex Uptodate 16
  • 17. Clinical Manifestation of NTM Disease  Pulmonary disease (most common )  Especially in older persons  M. avium complex (MAC), M. kansasii, M. abscessus  Probably acquired by aerosol inhalation  Superficial lymphadenitis  Especially cervical lymphadenitis  Children: MAC, M. scrofulaceum  Skin and soft tissue infection  Usually as a consequence of direct inoculation  M. marinum, M. ulcerans, RGM spp  Disseminated disease  HIV infection Am J Respir Crit Care Med. 2007;175:367–416. 17
  • 18. Predisposing factors to NTM lung infection  Underlying lung disease and altered mucociliary clearance  COPD, bronchiectasis, cystic fibrosis, pneumoconiosis, previous TB, esophageal motility disorders  Immune deficiency  HIV infection: reduced CD4 T-lymphocyte (usually <100/μL)  Defects in IFN- γ, IL-12, TNF-α  Immunosuppressive drugs  Other underlying conditions  Malignancy, alcohol abuse Am J Respir Crit Care Med. 2007;175:367–416. 18
  • 19.  Increased NTM isolation and decreased TB isolation  From 32.3% to 49.8% (p<0.05)  Increased disease incidence, predominately pulmonary NTM disease  All NTM disease: from 2.7 to 10.2 per 100,000 pt (p<0.0001)  Pulmonary NTM disease: from 1.26 to 7.94 per 100,000 (p= 0.0194) Emerg Infect Dis. 2010 Feb;16(2):294-6. Epidemiologic Trends of NTM in Taiwan 2000-2008 TB NTM Prevalence of isolates Incidence of NTM disease Pulmonary All Extrapulmonary 19
  • 20. NTM species causing pulmonary infection in Asia Distribution of NTM species varies by geographic region Emerg Infect Dis. 2011 Mar;17(3):343-9. Taiwan 1. MAC 2. M. abscessus (RGM) 20
  • 21. Chang Gung Med J. 2009 Sep-Oct;32(5):499-508. Characteristics of Patients with NTM Pulmonary Diseases Southern vs. Northern Taiwan Predominantly male, elderly, pre-existing lung disease. 21
  • 22.  Rapid-growth species and MAC appear to be the major NTM species in Taiwan Chang Gung Med J. 2009 Sep-Oct;32(5):499-508. Pathogens of NTM pulmonary disease Southern vs. Northern Taiwan 22
  • 23. Symptoms of NTM lung disease  Variable and not specific symptoms, similar to TB  Cough (productive or dry)  Hemoptysis  Fever  Night Sweats  Weight loss and loss of appetite  Loss of energy  Others: shortness of breath, wheezing, and chest pain Am J Respir Crit Care Med. 2007;175:367–416. 23
  • 24. Clinical  Pulmonary symptoms  Chest radiograph or chest HRCT scan  Nodular or cavitary infiltrates, multifocal bronchiectasis  Exclusion of other diagnoses  Such as TB, malignancy, fungal disease Microbiologic  Recurrent positive culture results from sputum or bronchial wash  Transbronchial or other lung biopsy with mycobacterial histopathologic features  Granulomatous inflammation or AFB ATS: American Thoracic Society IDSA: Infectious Disease Society of America's Am J Respir Crit Care Med. 2007;175:367–416. ATS/IDSA Diagnostic Criteria for NTM lung disease Clinical, radiological, and microbiological all required 24
  • 25. Management of NTM Infection  Empiric therapy not recommended  Treatment guided by the isolated species  Species level indentification before proper treatment  Combination antibiotics  Susceptibility testing may not correlate to in vivo response in Slowly growing mycobacteria  Except − MAC- macrolide − M. kansasii- rifampin  Treatment duration  Negative culture maintained 1 year on therapy  Surgery management: localized infections and poor response to drug therapy Am J Respir Crit Care Med. 2007;175:367–416. Curr Opin Pulm Med. 2010 May;16(3):251-6. Expert Opin Pharmacother. 2012 May;13(7):967-86. Uptodate 25
  • 26. Treatment of NTM pulmonary disease Species Preferred regimen SGM MAC Nodular or bronchiectatic: TIW regimen Clarithromycin 1000mg/ Azithromycin 500-600mg Rifampin 600mg Ethambutol 25mg/kg Fibrocavitary, severe nodular/bronchiectatic: daily regimen Clarithromycin 500-1000mg/ Azithromycin 250mg Rifampin 600mg Ethambutol 15mg/kg ±Amikin/Streptomycin for the first 2 months M. kansasii Rifampin 600 mg/day Isoniazid 300 mg/day Ethambutol 15 mg/kg/day RGM M. abscessus Clarithromycin 500mg q12h/Azithromycin 200-500mg qd + Amikacin 7.5mg/kg bid + Cefoxitin 2g q4h/Imipenem 1g q6h M. fortuitum M. chelonae Treatment depend on susceptibility testing Amikacin, tobramycin,imipenem, cefoxitin, levofloxacin, TMP/SMX, doxycycline, clarithromycin, azithromycin Am J Respir Crit Care Med. 2007;175:367–416. Curr Opin Pulm Med. 2010 May;16(3):251-6. Expert Opin Pharmacother. 2012 May;13(7):967-86. Uptodate 26
  • 27. Summary  Prevalence and incidence of NTM increases  Patients with underlying diseases with chronic respiratory disease or immune deficiency are prone to develop NTM infections  Clinicians in taiwan should consider NTM as a possible cause of TB-like disease in these population 27
  • 28. Thank you for your attention

×