Alpha-1-Antitrypsin Deficiency in India and UAE | Complete Patient Guide

• CONFIRMED PHENOTYPE: Pi*ZZ, Pi*ZNull, Pi*SZ, or other severe AATD genotypes confirmed by serum AAT level (< 11 µmol/L or < 57 mg/dL by nephelometry) AND SERPINA1 genotyping or isoelectric focusing (IEF)

• PULMONARY ELIGIBILITY FOR AUGMENTATION: FEV1 15–65% predicted on spirometry; CT-documented emphysema (quantitative PD15 densitometry); non-smoker or smoking cessation confirmed ≥ 6 months; absence of IgA deficiency (risk of anaphylaxis to plasma products)

• LIVER DISEASE EVALUATION: All AATD patients require baseline liver assessment — serum LFTs, FibroScan® (liver stiffness ≥ 7 kPa warrants enhanced surveillance), abdominal ultrasound, and AFP for HCC screening in cirrhotic patients

• REQUIRED PRE-TREATMENT DIAGNOSTICS: Full pulmonary function tests (spirometry, body plethysmography, DLCO); HRCT thorax with quantitative densitometry; 6-minute walk test (6MWT) and SGRQ-C quality-of-life score; echocardiography (ECHO) to exclude pulmonary hypertension (RVSP > 40 mmHg modifies transplant candidacy); complete blood count, coagulation profile, serum protein electrophoresis; hepatitis B/C serology and HIV screening

• LIVER TRANSPLANT CANDIDACY (selected patients): MELD score ≥ 15 in AATD-related cirrhosis; Child-Pugh Class B or C; absence of active extrahepatic malignancy; psychosocial evaluation clearance

• LUNG TRANSPLANT CANDIDACY (end-stage): BODE index ≥ 7; FEV1 < 20% predicted; pO2 < 60 mmHg on room air; evaluation per ISHLT 2021 guidelines

• CONTRAINDICATIONS TO AUGMENTATION THERAPY: Selective IgA deficiency with known anti-IgA antibodies; active hypersensitivity to human plasma-derived proteins; Pi*MS or Pi*MZ phenotype without serum AAT deficiency (augmentation not indicated)

• RELATIVE CONTRAINDICATIONS: Active infection or sepsis (defer until resolved); severe decompensated heart failure (fluid load of IV infusion); pregnancy (insufficient safety data — risk-benefit discussion required)

STANDARD AAT AUGMENTATION THERAPY (INTRAVENOUS): Weekly IV infusion of purified, pasteurised, human plasma-derived alpha-1-antitrypsin concentrate at 60 mg/kg body weight, administered over 15–30 minutes in an outpatient or day-care setting. This is the only FDA-approved, EMA-approved disease-modifying therapy for AATD-related emphysema. The RAPID and RAPID-OLE trials (the only double-blind, placebo-controlled studies in AATD) demonstrated a 34% reduction in annual CT lung density loss (PD15 endpoint) and a significant benefit in FEV1 decline in the treatment arm over 4 years. Hospitals in India and the UAE offer all four internationally approved concentrates through verified cold-chain pharmaceutical procurement, with dose preparation handled by clinical pharmacists under aseptic conditions.

OPTIMISED COPD PHARMACOTHERAPY (CONCURRENT): AATD-related emphysema is managed alongside standard GOLD-guideline COPD therapy: dual bronchodilation with LABA/LAMA combinations (indacaterol/glycopyrronium, tiotropium/olodaterol), triple therapy (fluticasone furoate/umeclidinium/vilanterol) for frequent exacerbators, and PDE4 inhibitor roflumilast for chronic bronchitis phenotype. Mucolytics, pulmonary rehabilitation (minimum 20 supervised sessions), and non-invasive ventilation (NIV/BiPAP) for hypercapnic respiratory failure are integrated into the treatment plan.

LIVER-DIRECTED THERAPIES (INVESTIGATIONAL/COMPASSIONATE USE): For patients with significant hepatic polymer accumulation and liver fibrosis, emerging therapies include: (1) Fazirsiran (ARO-AAT) — subcutaneous RNAi agent targeting SERPINA1 hepatic mRNA, achieving 80–90% reduction in hepatic Z-AAT polymer in Phase 2 AROAAT2002 trial; available at select trial sites in India (AIIMS, CMC Vellore) and UAE (Cleveland Clinic Abu Dhabi); (2) NTLA-2002 — in vivo CRISPR base-editing therapy in Phase 1/2; (3) Carbamazepine — an autophagy enhancer that reduces hepatic Z-AAT accumulation, used off-label in paediatric AATD liver disease; (4) Small-molecule correctors (similar to CFTR corrector strategy for cystic fibrosis) in preclinical-to-Phase-1 development.

SURGICAL OPTIONS: Bronchoscopic Lung Volume Reduction (BLVR): For patients with severe heterogeneous emphysema (FEV1 20–45% predicted, RV > 175%, absence of collateral ventilation on Chartis assessment), endobronchial valve (EBV) placement — using Zephyr valves (Pulmonx) — achieves lobar atelectasis and functional improvement in FEV1 (mean +14.6% in LIBERATE trial). Available at advanced bronchoscopy centres in India (Apollo Hospitals, Medanta, Fortis) and the UAE (Mediclinic City Hospital Dubai, Cleveland Clinic Abu Dhabi).

Lung Transplantation: Bilateral sequential lung transplantation (BSLT) is the definitive treatment for end-stage AATD emphysema (FEV1 < 20% predicted, BODE ≥ 7). AATD is one of the top four indications for lung transplant worldwide. 5-year survival post-lung transplant in AATD is 50–60% (ISHLT registry), superior to idiopathic COPD. India's lung transplant programme (Apollo Chennai, Medanta Gurugram, Fortis Bangalore) has performed over 300 cases with outcomes comparable to international benchmarks. Post-transplant augmentation therapy is not required as the donor lungs produce normal AAT.

Liver Transplantation: For AATD-related end-stage liver disease (MELD ≥ 15, Child-Pugh C), orthotopic liver transplantation is curative — the donor liver produces normal AAT, correcting both the hepatic and (partially) the pulmonary deficiency. Living donor liver transplantation (LDLT) is widely available in India, reducing wait times significantly versus deceased-donor-only programmes.

PULMONARY REHABILITATION (STANDARD OF CARE): A minimum 8-week structured programme including aerobic training (treadmill, cycle ergometry at 60–80% peak work rate), inspiratory muscle training, and nutritional optimisation. Programmes at JCI-accredited centres in India and the UAE incorporate wearable monitoring (SpO2, heart rate) and telerehabilitation follow-up for international patients returning home.

PHASE 1 — PRE-ARRIVAL PREPARATION (2–4 weeks before travel):

• GAF Healthcare coordinates remote review of available medical records: serum AAT level, SERPINA1 genotype report, spirometry, HRCT chest, and liver function tests

• Hospital specialist team confirms eligibility and designs a personalised treatment protocol

• GAF Healthcare assists with e-Medical Visa application for India (typically approved within 3 business days) or facilitates UAE entry clearance

• Patient receives a detailed Pre-Travel Medical Pack: list of required fasting tests, medication reconciliation instructions, and travel health advisory

PHASE 2 — ARRIVAL & DIAGNOSTIC CONFIRMATION (Days 1–3):

• Day 1: Airport reception by GAF Healthcare's dedicated patient coordinator; transfer to accredited hospital or partner accommodation

• Day 1 afternoon: Admission for comprehensive baseline assessment — spirometry with bronchodilator response, body plethysmography, DLCO, 6MWT, ECHO, HRCT with quantitative densitometry (PD15 measurement), FibroScan® liver stiffness, complete blood panel, IgA level, serum protein electrophoresis, SERPINA1 genotype confirmation if not previously performed

• Day 2: Multidisciplinary team (MDT) review — pulmonologist, hepatologist, clinical geneticist, and clinical pharmacist — to confirm diagnosis, phenotype, treatment eligibility, and therapy selection

• Day 3: MDT report presented to patient; written informed consent obtained; therapy schedule confirmed

PHASE 3 — THERAPY INITIATION (Days 4–7):

• Day 4: First IV AAT augmentation infusion administered under supervised conditions (15–30 min infusion, 1-hour post-infusion observation for hypersensitivity reactions — fever, urticaria, anaphylaxis risk < 0.1% per infusion)

• Pre-medication protocol: paracetamol and antihistamine administered 30 minutes before infusion as per institutional protocol

• Vital signs (BP, SpO2, HR, temperature) monitored continuously during infusion and for 60 minutes post-infusion

• Day 5–6: Patient education sessions — infusion technique (for future home infusion if appropriate), exacerbation recognition, action plans, inhaler optimisation, pulmonary rehabilitation introduction

• Day 7: Second infusion if tolerated; repeat safety bloods (LFTs, FBC); physician review and travel clearance assessment

PHASE 4 — RECOVERY & FIT-TO-FLY ASSESSMENT (Days 8–14):

• Patients who tolerate the first two infusions without adverse reactions are typically cleared for international travel by Day 10–14

• Flight fitness is confirmed by the treating pulmonologist: SpO2 ≥ 92% on room air at rest, no acute exacerbation, stable haemodynamics

• Patients with baseline SpO2 < 92% require a formal hypoxia altitude simulation test (HAST) to determine in-flight oxygen requirements

• GAF Healthcare provides a comprehensive Medical Summary Report and a referral letter to the patient's home physician outlining the ongoing infusion schedule (60 mg/kg IV weekly), monitoring parameters (spirometry every 6 months, HRCT annually, FibroScan® annually), and emergency contact protocols

PHASE 5 — LONG-TERM ONGOING THERAPY:

• Augmentation therapy is lifelong; GAF Healthcare coordinates with home-country infusion centres or assists with periodic return visits to India or UAE for annual monitoring

• Annual follow-up visit (1 week duration) recommended: repeat quantitative CT densitometry, spirometry, DLCO, 6MWT, liver assessment, and MDT review

• Telemedicine follow-up consultations available through GAF Healthcare's partner network at 3-month intervals

• Patients listed for lung or liver transplant undergo additional evaluation phases per ISHLT/ILTS guidelines