Alpha 1-antitrypsin deficiency medical therapy: Difference between revisions

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{{Alpha 1-antitrypsin deficiency}}
{{Alpha 1-antitrypsin deficiency}}
{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}
{{CMG}}; {{AE}}{{Mazia}}


==Overview==
==Overview==
Alpha 1-antitrypsin deficiency (A1AD) may be treated through intravenous infusions derived from donated human plasma.
[[Treatments|Treatment]] guidelines for AATD include [[Alpha antitrypsin|alpha 1 antitrypsin]] [[enzyme]] repletion, [[smoking cessation]], [[Bronchodilators|long-acting inhaled bronchodilators]], [[Vaccinations|preventive vaccinations]] against [[influenza]] and [[pneumococcus]], [[pulmonary rehabilitation]] for [[patients]] with functional impairment, [[Oxygen|supplemental oxygen]] if needed [[lung transplantation]], treatment of [[COPD exacerbation resident survival guide|COPD exacerbation]] in all patients of AATD should include AAT repletion.


==Medical Therapy==
==Medical Therapy==
In the United States, Canada, and several European countries, lung-affected A1AD patients may receive intravenous infusions of alpha-1 antitrypsin, derived from donated human plasma. This augmentation therapy is thought to arrest the course of the disease and halt any further damage to the lungs. Long-term studies of the effectiveness of A1AT replacement therapy are not available. It is currently recommended that patients begin augmentation therapy only after the onset of emphysema symptoms.
* Across developed countries, A1AD patients presenting with [[Pulmonary|pulmonary symptoms]] may receive [[intravenous infusion]] of [[alpha-1 antitrypsin]], derived from donated [[human plasma]]. This augmentation [[therapy]] arrests the course of the [[disease]] and halts any further damage to the [[lungs]]. It is recommended that [[patients]] must begin augmentation therapy only after the onset of [[emphysema]] [[symptoms]].<ref name="pmid19707408">{{cite journal |vauthors=Petrache I, Hajjar J, Campos M |title=Safety and efficacy of alpha-1-antitrypsin augmentation therapy in the treatment of patients with alpha-1-antitrypsin deficiency |journal=Biologics |volume=3 |issue= |pages=193–204 |year=2009 |pmid=19707408 |pmc=2726081 |doi= |url=}}</ref><ref name="pmid28496314">{{cite journal |vauthors=Edgar RG, Patel M, Bayliss S, Crossley D, Sapey E, Turner AM |title=Treatment of lung disease in alpha-1 antitrypsin deficiency: a systematic review |journal=Int J Chron Obstruct Pulmon Dis |volume=12 |issue= |pages=1295–1308 |year=2017 |pmid=28496314 |pmc=5422329 |doi=10.2147/COPD.S130440 |url=}}</ref>


Augmentation therapy is not appropriate for liver-affected patients; treatment of A1AD-related liver damage focuses on alleviating the symptoms of the disease. In severe cases, liver transplantation may be necessary.
* Augmentation therapy is not recommended for [[liver]]-affected patients; [[Treatments|treatment]] of A1AD-associated [[liver damage]] focuses on symptomatic relief. In severe cases, [[liver]] [[transplantation]] may be necessary.


As α<sub>1</sub>-antitrypsin is an [[acute phase reaction|acute phase reactant]], its [[Transcription (genetics)|transcription]] is markedly increased during [[inflammation]] elsewhere in response to increased [[interleukin]]-1 and 6 and [[Tumor necrosis factor-alpha|TNFα]] production. Any treatment that blunts this response, specifically [[paracetamol]] (acetaminophen), can delay the accumulation of A1AT polymers in the liver and (hence) [[cirrhosis]]. A1AD patients are therefore encouraged to use paracetamol when slightly to moderately ill, even if they would otherwise not have used [[antipyretic]]s.
* α<sub>1</sub>-antitrypsin is an [[acute phase reaction|acute phase reactant]]. Its [[Transcription (genetics)|transcription]] is markedly increased during [[inflammation]] as a result of increased [[interleukin]]-1 and 6 and [[Tumor necrosis factor-alpha|TNFα]] production. Any treatment that blunts this response, for example [[acetaminophen]], can delay the accumulation of A1AT [[polymers]] in the [[liver]] and resultant [[cirrhosis]]. A1AD patients are therefore encouraged to use [[acetaminophen]] when ill, even if they do not need [[antipyretics]].
 
*[[Treatments|Treatment]] guidelines for AATD include:
**[[Alpha antitrypsin|Alpha 1 antitrypsin]] [[enzyme]] repletion
**[[Smoking cessation]]
**[[Bronchodilators|Long-acting inhaled bronchodilators]]
**[[Vaccinations|Preventive vaccinations]] against [[influenza]] and [[pneumococcus]]
**[[Pulmonary rehabilitation]] for [[patients]] with functional impairment
**[[Oxygen|Supplemental oxygen]] if needed
**[[Lung transplantation]]
*[[Treatments|Treatment]] of [[Chronic obstructive pulmonary disease|COPD exacerbation]] in all [[patients]] of AATD should include AAT repletion.
* '''1 Alpha 1-antitrypsin deficiency (A1AD)'''
** 1.1 A'''ssociated lung disease'''
*** 1.1.1 '''Adult'''
**** Preferred regimen (1): Purified pooled [[human plasma]] [[alpha 1-antitrypsin]] 60 mg/kg/wk iv 
**** Preferred regimen (2): Short-acting [[Beta-adrenergic|beta-adrenergic agents]] and [[ipratropium bromide]] [[Bronchodilators|bronchodilator]] [[Metered-dose inhaler|MDI]]
**** Preferred regimen (3): [[Corticosteroid medications|Inhaled corticosteroids]]
**** Alternative regimen (1): Alpha1-proteinase inhibitors such as Prolastin-C, Aralast NP, Glassia, Zemara 
**** Alternative regimen (2): [[Beta-adrenergic-blocking agents|Long-acting beta-adrenergic agents]] [[Metered-dose inhaler|MDI]] 
**** Alternative regimen (2): [[Theophylline|Oral theophylline]]
**** Alternative regimen (3): [[Corticosteroids|Oral corticosteroids]]
*Augmentation therapy is the specific therapy for Alpha 1-antitrypsin deficiency (A1AD) associated [[lung disease]].
*Augmentation therapy includes [[intravenous infusion]] of purified pooled [[human plasma]] [[alpha 1-antitrypsin]] to raise and maintain serum Alpha 1-antitrypsin levels above the threshold and to slow [[emphysema]] progression and enhance the duration and quality of life.
*Food and Drug Administration has approved four preparations of purified AAT.
*Following infusion AAT levels remain above the protective threshold for most of the dosing interval.
*The infused AAT has the ability to neutralize [[neutrophil elastase]] activity.
*Augmentation therapy recipients demonstrate a slower rate of FEV1 decline than nonrecipients.
*Wencker and colleagues conducted a before-after study and found that the greatest effect of augmentation therapy in changing FEV1 slope was observed in individuals with a rapid FEV1 decline before augmentation therapy was initiated (ie, FEV1 decline 256 mL/y before therapy vs 53 mL/y during therapy).
 
*[[Bronchodilators]] are used for symptomatic relief of airflow obstruction and symptoms resulting from AATD and associated [[emphysema]].
*[[Antibiotics]] can be used to treat [[Bacterial|bacterial complications]], such as [[pneumonia]] or [[Bronchitis|purulent bronchitis]].
*[[Bronchodilators]] and [[antibiotics]] do not have any effect on [[disease]] progression.
*[[Corticosteroids]] can be used for short-term relief but have no proven long-term benefit in inhaled or oral preparations.
*Avoid [[oral steroids]] because of their long-term adverse effects.
*[[Oxygen]] is prescribed if [[patients]] are [[Hypoxemia|hypoxemic]] at rest or with activity.
*Replacement/Augmentation [[therapy]] is indicated to slow the progression of [[emphysema]].
*Currently, IV augmentation therapy is the only FDA-approved [[Treatments|treatment]] specific for AATD. It is indicated for patients with moderate degrees of airflow obstruction (FEV1 35-65% of predicted).
*Recommended [[dosage]] and [[route of administration]] is, 60 mg/kg/wk given IV.
*[[Respiratory]] [[enzymes]] are drugs used for long-term replacement in [[patients]] with [[clinical]] [[emphysema]].
*Alpha1-proteinase [[inhibitor]] like Prolastin-C, Aralast NP, Glassia, Zemara is available for use in the United States.
*[[Respiratory]] [[enzymes]] are prepared from pooled [[human]] [[plasma]] by using a cold [[alcohol]] fractionation process followed by further [[purification]] steps to obtain a sterile, stable, [[lyophilized]] preparation of purified [[human]] alpha1-antiprotease inhibitor.
*[[Plasma]] is tested for [[HIV]], [[hepatitis B]], and [[hepatitis C]] before adding it to the product.
*In order to reduce the potential [[Risk Stratification Tools|risk]] of [[infectious]]-agent transmission, the solvent detergent mixer is added to the product, which serves to inactivate the [[viral]] agents
* the main goal of [[medical]] [[therapy]] is to slow down or halt the progression of [[lung]] [[disease]] in AATD.
*The most effective [[Treatments|treatment]] approach is to quit [[smoking]], associated with the greatest effect on [[Survival rates|survival]] of [[patients]] with AATD.
*Strategies to help and motivate [[patients]] to quit [[smoking]] include:
**Inform [[patients]] about the consequences of [[smoking]] on AATD
**Inquire about their [[smoking]] habits
**Advice the [[patients]] to quit [[smoking]]
**Assist [[patients]] to quit [[smoking]] with encouragement, [[education]] and [[nicotine]] replacement.
**Follow-up with these [[patients]].
 
* Improving [[lung]] [[Function (biology)|function]]:
**Efforts should be made to improve [[lung]] [[Function (biology)|function]] in [[patients]] with AATD associated [[emphysema]].
**Administration of short-acting [[beta-adrenergic]] agents and [[ipratropium bromide]] [[bronchodilator]] can help maximize [[lung]] [[Function (biology)|function]]. The preferred route of administration is metered-dose [[inhalers]] because they have a lower [[incidence]] of [[adverse effects]] than other [[Routes of administration|routes]]. These [[drugs]] have no long-term effect on [[disease]] progression.
**[[Corticosteroids|Inhaled corticosteroids]] provides symptomatic relief in [[patients]] with frequent exacerbations. [[Adverse effect]] includes [[infection]].
**[[Beta-adrenergic-blocking agents|Long-acting inhaled beta-adrenergic drugs]] and [[anticholinergics]] improve [[bronchodilation]] in the [[patient]] [[population]] with AATD.
**Reserve [[Corticosteroids|oral corticosteroids]] for acute exacerbations with increased [[cough]] and [[sputum]].
**Long-term [[Corticosteroids|corticosteroid]] use is associated with many detrimental adverse effects. Limit [[oral]] [[steroid]] use to brief courses of 1-2 weeks. Start [[therapy]] to prevent [[osteoporosis]] when long courses are administered.
**A therapeutic trial of [[theophylline]] may be indicated for selected [[patients]]. [[Theophylline]] administration requires frequent monitoring of serum levels as it has a narrow therapeutic range and its [[metabolism]] is frequently altered by other [[drugs]] or [[Illnesses|illness]], which can lead to episodes of [[drug toxicity]]. [[Theophylline]] is [[metabolized]] by the [[liver]]. [[Smoking]] increases the [[metabolism]] of [[theophylline]].


==References==
==References==
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{{reflist|2}}
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Latest revision as of 18:02, 22 January 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mazia Fatima, MBBS [2]

Overview

Treatment guidelines for AATD include alpha 1 antitrypsin enzyme repletion, smoking cessation, long-acting inhaled bronchodilators, preventive vaccinations against influenza and pneumococcus, pulmonary rehabilitation for patients with functional impairment, supplemental oxygen if needed lung transplantation, treatment of COPD exacerbation in all patients of AATD should include AAT repletion.

Medical Therapy

References

  1. Petrache I, Hajjar J, Campos M (2009). "Safety and efficacy of alpha-1-antitrypsin augmentation therapy in the treatment of patients with alpha-1-antitrypsin deficiency". Biologics. 3: 193–204. PMC 2726081. PMID 19707408.
  2. Edgar RG, Patel M, Bayliss S, Crossley D, Sapey E, Turner AM (2017). "Treatment of lung disease in alpha-1 antitrypsin deficiency: a systematic review". Int J Chron Obstruct Pulmon Dis. 12: 1295–1308. doi:10.2147/COPD.S130440. PMC 5422329. PMID 28496314.


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