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Panbronchiolitis - Diffuse (1 of 3)

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Panbronchiolitis - Diffuse (1 of 3) Panbronchiolitis - Diffuse (1 of 3) 1 Patient presents w/ signs & symptoms suggestive of diffuse panbronchiolitis 2 DIAGNOSIS 3 Is diff use No ALTERNATIVE panbronchiolitis DIAGNOSIS confi rmed? Yes A Pharmacological therapy • Macrolides B FOLLOWUP Does patient show favorable response to treatment after Yes 6 mth? No CONTINUE TREATMENT REASSESS TREATMENT FOR 2 YR OR >2 YR FOR RESPONSE, MAY SHIFT PATIENTS W/ RESP FAILURE TO OTHER MACROLIDES 1 DIFFUSE PANBRONCHIOLITIS (DPB) Defi nition • Infl ammatory disease aff ecting the respiratory bronchioles • Causes progressive suppurative & obstructive respiratory disease • is is an idiopathic disease which is primarily found in Japan, Korea & China • Predisposition to the disease may be genetically-related but environmental factors should also be considered • Failure to treat DPB leads to development of widespread bronchiectasis, progressive respiratory failure & death Epidemiology • More common in 2nd-5th decade of life • Not related to smoking & exposure to toxic fumes • High incidence in Asian countries (Japan, Korea, Taiwan, Malaysia, China, ailand, Singapore) Signs & Symptoms • Chronic paranasal sinusitis (>80%) • Productive cough which usually occurs in the 2nd-5th decade of life • Wheezing© MIMS • Dyspnea on exertion Not all products are available or approved for above use in all countries. Specifi c prescribing information may be found in the latest MIMS. A1 © MIMS 2019 Panbronchiolitis - Diffuse (2 of 3) 2 DIAGNOSIS Physical Exam • Crackles, wheezing on chest exam Pulmonary Functions Tests • Spirometry, lung volume determination - May show signifi cant obstructive defect w/ or w/o superimposed restriction - Signifi cantly limited airways resistant to bronchodilators - FEV1/FVC <70%, vital capacity (VC) <80%, residual volume (RV) >150% - Hypoxemia may be present in blood gas analysis Panbronchiolitis - Diffuse Panbronchiolitis • P. aeruginosa infection, reduced pulmonary diff using capacity, progression of hypoxemic state & subsequent hypercapnia seen in advanced stages of DPB Imaging Studies • Chest X-ray (CXR) - May show pulmonary hyperinfl ation & diff use bilateral small nodular shadows - Findings of bronchiectasis (ring-shaped/tram-line shadows) may be seen in advanced disease • High-resolution computerized tomography (HRCT) - Bilateral & symmetric centrilobular nodules forming a “tree-in-bud” pattern, - Bronchiolectasis - Mosaic air trapping on lung periphery Histopathologic Findings • Presence of foamy histiocytes in bronchiolar & peribronchiolar infi ltrates • Transmural & peribronchiolar infi ltrations by lymphocytes, plasma cells, & histiocytes Microbiology/Hematology • Sputum analysis • Cold agglutinins are elevated in patients w/ DPB Invasive Exam • Eg bronchoscopy w/ lavage, surgical lung biopsy • Done to confi rm the diagnosis if fi ndings of the radiographic studies are non-specifi c • Bronchiolar infl ammation w/ transmural infi ltrates of lymphocytes, plasma cells, & foam cells are seen in lung biopsy • Fluid obtained via bronchoscopy often reveals increased lymphocytes & neutrophils Diagnostic Criteria for DPB by Ministry of Health & Welfare of Japan • Diagnosis of DPB is defi nite if the fi rst 3 & at least 2 of the last 3 criteria are present - Presence of persistent cough, sputum production & dyspnea on exertion - History of chronic paranasal sinusitis - CXR shows bilateral diff use small nodular shadows, or chest CT scan w/ centrilobular micronodules - Presence of coarse crackles, occasional rhonchi, wheezes or squawk on physical exam - FEV1/FVC <70% & PaO2 <80 mmHg - Cold haemmaglutinin titre ≥64 3 ALTERNATIVE DIAGNOSIS • Bronchiectasis • Allergic bronchopulmonary aspergillosis (ABPA) • Bronchiolitis (infectious) • Obliterative bronchiolitis • Chronic bronchitis • Sarcoidosis • Cystic fi brosis • Mycobacterium Avium complex pulmonary infection • Hypogammaglobulinemia • Churg-Strauss syndrome • Primary ciliary dyskinesia • Wegener’s granulomatosis A PHARMACOLOGICAL THERAPY • Macrolides should be started as soon as diagnosis is established Macrolides • Eg Erythromycin,14 member-ringed macrolides (ie Clarithromycin, Roxithromycin), & the 15 member-ringed macrolide Azithromycin • Erythromycin is the 1st choice in treatment of DPB - Treatment duration is for at least 6 mths • Other macrolides© (Clarithromycin, Roxithromycin,MIMS Azithromycin) are used when Erythromycin is ineff ective or not tolerated Not all products are available or approved for above use in all countries. Specifi c prescribing information may be found in the latest MIMS. A2 © MIMS 2019 Panbronchiolitis - Diffuse (3 of 3) A PHARMACOLOGICAL THERAPY (CONT’D) Macrolides (Cont’d) • Studies show better lung function (decreased dyspnea, opacities in HRCT) w/ Azithromycin use in patients w/ DPB Actions: • Inhibit production of pro-infl ammatory cytokines & formation of leukotriene B4 • Block the formation of adhesion molecules required for migration of neutrophils E ff e c t s : • Decreased infl ammation of the airways, leading to improved pulmonary function & decreased infection • Panbronchiolitis - Diffuse Panbronchiolitis Erythromycin helps improve host defense & regulate bacterial activities B FOLLOW-UP • Follow up & assess patient’s overall clinical response after 6 mth of macrolide treatment • If patient shows good response w/ macrolide, ie pulmonary function, clinical, radiological fi ndings have improved, complete the treatment for 2 yr • If symptoms recur after stopping the treatment, resume medication • In patients w/ respiratory failure & extensive bronchiectasis, continue treatment for >2 yr Dosage Guidelines MACROLIDES Drug Dosage Remarks Azithromycin 500 mg PO 24 hrly x 3 days Adverse Reactions or • GI eff ects (N/V, abdominal discomfort, diarrhea, 500 mg PO 24 hrly on the 1st day, pseudomembranous colitis, constipation); CNS then 250 mg PO 24 hrly x 4 days eff ects (dizziness, vertigo, headache); CV eff ects (cardiotoxicity, palpitation, chest pain); GU tract Clarithromycin Adult: 250-500 mg PO 12 hrly x (monilia, vaginitis, nephritis); Other eff ects 7-14 days (candidal infections, fatigue, skin rash, or photosensitivity, angioedema) 500 mg IV 12 hrly x 2-5 days • Azithromycin, Roxithromycin & Clarithromycin Childn: 7.5 mg/kg PO/IV 12 hrly tend to cause less GI disturbances than Erythromycin Erythromycin Adult: 250 mg PO 6 hrly Special Instructions or • Erythromycin & Azithromycin may be taken w/ 500 mg PO 12 hrly food to decrease gastric distress; Roxithromycin Childn: 30-50 mg/kg/day PO in should be taken at least 15 min before meals 3-4 divided doses • Use w/ caution in patients w/ renal or hepatic Roxithromycin Adult: 150 mg PO 12 hrly or dysfunction & pseudomembranous colitis 300 mg PO 24 hrly • Avoid concomitant use w/ aluminum-/magnesium Childn: 5-8 mg/kg/day PO in salt-containing antacids 2 divided doses All dosage recommendations are for non-pregnant & non-breastfeeding women, & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. ©Not all products areMIMS available or approved for above use in all countries. Products listed above may not be mentioned in the disease management chart but have been placed here based on indications listed in regional manufacturers’ product information. Specifi c prescribing information may be found in the latest MIMS. Please see the end of this section for reference list. A3 © MIMS 2019.
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