Deficitul de alfa 1 antitripsina

1. Monitorizarea funcției
pulmonare și a calității vieții în
DAAT
Emanuela Tudorache, Diana Manolescu, Cristian Oancea
Universitatea de Medicină şi Farmacie Victor Babeş, Timişoara

2. Alpha 1-antitrypsin deficiency (A1AD)
genetic disorder that causes defective production of
A1AT, leading to decreased A1AT activity in the blood
and lungs and deposition of excessive abnormal A1AT
protein in liver cells .
=> severe A1AT deficiency causes :
• Emphysema,
• COPD ,
• Bronchiectasis with early onset (before 45 years of
age)
• Others (Asthma, Cirrhosis, Wegener’s Granulomatosis,
Pancreatitis, Gallstones, Autoimmune hepatitis )

4. Alpha 1-antitrypsin deficiency
Prevalence :
• People of northern European, Iberian ancestry are at the highest risk for
A1AD.
• 4% of world population carry the PiZ allele;
• between 1 in 625 and 1 in 2000 are homozygous
• 1−5% of patients with emphysema
• 8.20% of patients with COPD are carriers of a modified gene
• The character of the mutation does not determine the clinical picture of
the pulmonary disease and individuals with identical deficiency genotype
may develop highly varied complications within respiratory system.
Ruxandra Ulmeanu, Ana Nebunoiu et al, Alpha 1 antitrypsin deficiency in Romania:
preliminary results from the genetic screening 2012-2015, unpublished data

5. Why testing for Alpha 1-antitrypsin deficiency ?
These forms are more severe, with frequent
exacerbation that have a modest response to standard
treatment and accelerated deterioration of the lung
function.
The specific treatment for this disease (intravenous
A1AT substitution) is still not available in Romania.

6. Alpha 1-antitrypsin deficiency
The “ugly” sister of classical
COPD

7. Lung Function
• Spirometry
• Chest x-ray
• CT - lung densitometry
• Induced sputum
• DLCO, FeNO
• diaphragmatic US
• 6MWD, Cycloergometry, Submaximal
exercise testing
• Pulsoximetry in static and dynamic -
Oxygen therapy LOTT
Influenced by :
• Rate and severity of exacerbations
• Therapy management:
• Augmentation therapy: intravenous
alpha-1 antitrypsin substitution
benefits and side effect
• Bronchodilators: relieve coughing
• Inhaled Corticosteroids
• Antibiotics- in respiratory infections
• Influenza and Pneumococcal vaccination
• Lung transplant-in severe cases

8. Quality of Life
• HRQL: SGRQ, CAT, MRC, ACT
• Evaluation of Activities of Daily Living (ADL)
• Comorbidities
• Smoking cession
• Pulmonary Rehabilitation, Inspiratory muscle training and breathing
techniques
• Medical Education
• Family /Community Support
• Nutrition

17. Normal physical activity in healthy people

18. Normal physical activity in healthy people

19. Physical activity in COPD patients

20. Physical activity in COPD patients

21. Muscle loss
Decrease in thickness of quadriceps and increase of perimuscular adipose
component .
Normal subject vs. COPD stage IV

22. Diaphragmatic US

23. Breath training

24. Program type Advantages Disadvantages
In-patient Intensive
Safe
Cost
Family exclusion
Out-patient Economic
Safe
Movement
Community Close to home
Development potential
Availability of personnel
Quality of supervision
Home patient Household relevance Cost
Without group therapy
effect
Pulmonary Rehabilitation Program types

25. This observational study included 422 patients with severe AATD enrolled in
the Italian AATD Registry.
Inclusion criteria: the presence of severe AAT deficiency, defined by the
carriage of the PI*ZZ genotype, PI*SZ genotype or another rare severe deficient
or null genotypic variant.

28. Background—The relationship between quantitative airway measurements on computed
tomography (CT) and airflow limitation in individuals with severe α1-antitrypsin deficiency (AATD)
is undefined.
Conclusions—Quantitative airway measurements are significantly correlated with airflow
limitation in AATD, particularly in the distal airways of right upper lobe. Emphysema of the lower
lung is the predominant component.

30. This study shows a mean annual deterioration of SGRQ score of ~1.2 units in the
whole population. In non-AATD COPD, two studies reported a deterioration of ~0.06
units per year.

34. In summary, our results indicate that the questionnaires
evaluated are useful to monitor the severity and
impairment in health status in patients with emphysema
due to AATD. The scores of these questionnaires are
more closely related to the usual measures of severity
of lung function impairment in patients with AATD
compared with individuals with non-AATD COPD. This
probably reflects the particular characteristics of the
disease in carriers of this deficiency, who are typically
younger, with fewer co-morbidities and lower smoking
consumption.

35. Based on the metric of “time to desaturate
to less than or equal to 88%” during a
6MWT test, those with severe deficiency
of AAT desaturated sooner.
In summary, AAT-deficient subjects in
LOTT demonstrated more pronounced
exercise desaturation than matched LOTT
subjects with usual COPD.

36. Despite this, the RAPID/RAPID Extension program has provided evidence of a reduction in the rate of lung
density decline and a disease-modifying effect of A1-PI therapy in patients with AATD [21, 22], with
possible implications for long-term changes in mortality. These findings suggest that the early introduction
of treatment in patients with severe emphysema-related AATD may delay the time to death, lung
transplantation or crippling respiratory complaints.

38. In conclusion ….

39. Thank you !