How we monitor and manage lung disease in primary antibody deficiencies (PAD)

Routine monitoring
 Putative extrapulmonary predictors of GLILD (splenomegaly, autoimmunity, liver disease, B-cell flow-cytometric typing according to EUROclass trial) are routinely assessed in all PAD patients and reported in the medical record
 Spirometry before and after bronchodilator administration (eventual methacholine challenge test) at diagnosis and annually
DLCO measurement annually
 Blood gas analysis as conventionally indicated
 HRCT: at diagnosis (if not recently performed) and every 5 years. HRCT is part of the initial evaluation aimed to a tailored therapeutic approach that includes the choice of Ig replacement therapy dosage, route and frequency of administration, the eventual adjunct of an antibiotic prophylaxis and/or need for pulmonary rehabilitation and exercise training
 Lung MRI: currently under evaluation as radiation-sparing imaging technique [142, 143]
Acute infection
 Sputum examination or bronchoalveolar lavage may be useful for a precise microbiological diagnosis, in order to drive optimal antibiotic treatment
 Waiting for a defined diagnosis, a broad-spectrum oral antibiotic course is prescribed, according to personal history of allergy, previous evidence of antibiotic resistance and eventual ongoing macrolide prophylaxis
Obstructive lung disease
 Patients are usually prescribed a combined steroid/LABA topical treatment
 In case of bronchiectasis documented by HRCT, prophylactic azithromycin is prescribed (250 mg per day, three consecutive days per week)
 Pulmonary rehabilitation and exercise training are recommended to patients displaying bronchiectasis on HRCT scan
 Bronchoalveolar lavage (e.g. lobar lavage) may also be a mechanistic therapeutic adjunct in selected patients with bronchiectasis
ILD suspicion (cough, dyspnoea on exertion, DLCO reduction, restrictive PFT pattern)
 6MWT as first choice exercise testing
 HRCT scan repetition
 If signature of ILD emerging, records are discussed during the ILD MDT meeting
 Bronchoscopy is in most cases the first invasive step, both for microbiology and BALF cytology, with lymphocytes sub-population analysis if lymphocytosis is reported
 A trans-bronchial biopsy or mediastinoscopy is considered if a lymphoproliferative disease has to be ruled out
 Open lung or VATS biopsy is performed if a specific treatment has to be established. In case of signs or symptoms of extrapulmonary disease, PET/CT or PET/MRI imaging is performed, in order to assess different organ involvement and provide alternative sites for a bioptic approach
 Treatment: asymptomatic patients may undergo improvement of IgG replacement level, aiming at higher trough levels, even without a previous surgical lung biopsy. In case of concomitant bronchiectasis, prophylactic azithromycin is prescribed, if not already ongoing. Symptomatic patients are started on steroid treatment (20–40 mg of prednisone, as for sarcoidosis). If first-line treatment fails or steroids are contraindicated, combined rituximab-azathioprine treatment is prescribed

GLILD: granulomatous-lymphocytic interstitial lung disease; DLCO: diffusing capacity of the lung for carbon monoxide; HRCT: high-resolution computed tomography; Ig: immunoglobulin; MRI: magnetic resonance imaging; LABA: long-acting β-agonist; PFT: pulmonary function test; 6MWT: 6-min walk test; ILD: interstitial lung disease; MDT: multi-disciplinary team; BALF: bronchoalveolar lavage fluid; VATS: video-assisted thoracoscopic surgery; PET; positron emission tomography; CT: computed tomography.