Obstructive lung disease

Question 1

Bronchiectasis

Answer 1

Diagnosis

• HRCT criteria: (1) internal dia of bronchus is > than the accompanying vessel. (2) bronchus fails to taper in the periphery. (3) airway wall thickening, but this is also found in asthma and COPD

Pathophys:

• Bacterial colonization –> neutrophil inflammation –> airway destruction –> abnormal mucous clearance –> cycle repeats

HSCT can be associated with development of bronchiectasis. Majority of patients in studies are shown to have concurrent GVHD.

Treatment

• Systemic corticosteroids are not used in pts with non-CF bronchiectasis
• ICS may improve dyspnoea/cough/beta-agonist use, but have not been shown to improve lung function or exaccerbation frequency in bronchiectasis, and are associated w adverse effects of steroids (osteoporosis, cataracts)
• Macrolides are immunomodulatory but don’t cause immunosupression. They modify mucous production, inhibit biofilm, suppress inflamm mediators, moderate white cell recruitment. Lead to reduced # exacc, sputum volume, improved well-being.
• 3 x large trials RE effect of macrolides on non-CF bronchiectasis: EMBRACE trial showed that pts on thrice weekly azithro 500mg for 6mo had 62% relative reduction in rate of exacc compared w placebo; a reduction in symptoms at 6months but not 12mo; no difference in FEV1; reduction in CRP/WCC.

BAT trial showed that pts on 250mg azithro thrice weekly for 12mo had lower median # of exacc; prolonged time to first exacc; very mild improvement in FEV1

• risks of chronic macrolide use inc promoting growth of macrolide-resistant NTM. Need to rule out NTM prior. Macrolides may also lead to prolonged QT.

https://www.atsjournals.org/doi/full/10.1164/rccm.201303-0411CI (2013, ATS journals Bronchiectasis)

Question 2

ABPA

Answer 2

Description:

• Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction in response to colonization of the airways with Aspergillus fumigatus that occurs almost exclusively in patients with asthma (1-5% asthmatics) or cystic fibrosis (1-9% CF pts)
• characterized pathologically by mucoid impaction of the bronchi, eosinophilic pneumonia, and bronchocentric granulomatosis in addition to the histologic features of asthma

Pathogen:

• exposure of atopic individuals to fungal spores or mycelial fragments results in the formation of IgE and IgG antibodies.
• T cells also play an important role in ABPA. There are increases in Th2 CD4+ cell responses to Aspergillus antigens both in the bronchoalveolar lymphoid tissue and systemically. Aspergillus-responsive T cells generate cytokines interleukin (IL)-4, IL-5, and IL-13, which in turn account for the increases in blood and airway eosinophils and IgE in ABPA.
• Aspergillus colonization of the asthmatic airway leads to vigorous IgE- and IgG-mediated immune responses superimposed on the asthmatic milieu.
• Proteolytic enzymes and mycotoxins released by fungi, in concert with Th2-mediated eosinophilic inflammation and IL-8-mediated neutrophilic inflammation, may result in airway damage and central bronchiectasis.

Epidem:

• prevalence is 1-2%
• Rarely, ABPA occurs in patients with bronchiectasis, chronic granulomatous disease, hyperimmunoglobulinemia E, and in lung transplant recipients

Clinical features:

• recurrent exacerbations of asthma
• In severe cases, episodes of bronchial obstruction, fever, malaise, expectoration of brownish mucus plugs, and, at times, hemoptysis may occur. Wheezing is not always evident, and some patients present with asymptomatic pulmonary consolidation.
• A minority of patients have concomitant allergic aspergillus rhinosinusitis with symptoms of nasal congestion/obstruction, sinus pressure, and thick, dark-colored nasal discharge

Labs:

• Aspergillus is cultured from the sputum in up to two-thirds of patients with ABPA, but hyphae may not be seen by direct microscopy.
• elevated total blood eosinophil count (generally >500 cells/microL), elevated total serum IgE (generally >1000 IU/mL), precipitating IgG antibodies (precipitins - has sensitivity ~60%) to Aspergillus, and also specific IgE and IgG antibodies to Aspergillus (fumigatus) on immunoassay
• Expectorated sputum may contain “plugs” with eosinophils, Charcot-Leyden crystals, and may grow Aspergillus in culture
• Serum galactomannan is not useful in the identification of ABPA, but it is used to detect invasive aspergillosis infections

Imaging:

• Central bronchiectasis is a frequent feature and evidence of mucus plugging
• CXR: parenchymal opacities (usually involving the upper lobes), atelectasis due to mucoid impaction, and a number of findings characteristic of bronchiectasis
• HRCT: proximal cylindrical bronchiectasis with upper lobe predominance and bronchial wall thickening. Other findings include nodules, mucus plugging, tree-in-bud opacities, high attenuation mucus, atelectasis, peripheral airspace consolidation, or ground-glass attenuation, and possibly mosaic perfusion or air trapping

PFTs: Obstructive defect (or mixed pattern) with reduced FEV1, air trapping, increased RV, may or may not have post bronchodilator response. Some patients have reduced DLCO.

Diagnostic criteria:

• asthma or CF
• (2 of 3): specific IgE >0.35kU/L to aspergillus fumigatus and/or skin prick +ve to aspergillus and/or total IgE >1000 IU/mL
• (2 of 3): Aspergillus precipitins (precipitating asp. antibodies) present, or specific IgG to aspergillus fumigatus (more sensitive) >27mg/L and/or imaging c/w ABPA and/or total eosinophils >500cell/microL

Complications:

• acute invasive pulmonary aspergillosis
• aspergilloma
• chronic pulmonary aspergillosis
• Bronchiectasis and its complications

Treatment:

• systemic glucocorticoids (pred 0.5mg/kg/day tapering over 6wks - 3months) are the mainstay of treatment for acute ABPA
• therapy of acute or recurrent ABPA should consist of a combination of glucocorticoids and itraconazole [10]. Voriconazole is a reasonable alternative to itraconazole because it is better tolerated in some patients and is well absorbed.