Cystic fibrosis medical therapy: Difference between revisions

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{{Cystic fibrosis}}
{{Cystic fibrosis}}
==Overview==
==Overview==
[[Image:CFtreatmentvest2.JPG|thumb|left|250px|A typical breathing treatment for cystic fibrosis, using a mask nebuliser and the [[ThAIRapy Vest]]]]
 
The cornerstones of management for cystic fibrosis are treatment of [[respiratory tract infection|airway infection]], maximizing organ function, and encouragement of good nutrition and an active lifestyle.  The treatment for cystic fibrosis continues throughout a patient's life and aims to maintain quality of life. At best, current treatments delay the decline in organ function.
Medical treatments for patients with cystic fibrosis has targeted following consequences of the defect such as GI and pulmonary [[mucus]] plugging and infection. Treatment include [[Mucolytic agent|mucolytic agents]] ([[dornase alfa]], [[Acetylcysteine|N-acetyl-L-cysteine]]), [[airway]] surface [[rehydration]] ([[hypertonic]] [[Saline (medicine)|saline]], [[Osmosis|osmotic]] agents), [[Antimicrobial|anti-infective agents]] (for [[prophylaxis]], eradication of early [[infection]] and suppression of chronic [[infection]]), [[Anti inflammatory medications|anti-inflammatory agents]] ([[Non-steroidal anti-inflammatory drug|NSAIDs]], inhaled [[Corticosteroid|corticosteroids]], [[Leukotriene B4 receptor|LTB4 receptor]] [[Receptor antagonist|antagonists]] and [[Azithromycin]]) and potentiators of [[Cystic fibrosis transmembrane conductance regulator|CFTR protein]] defect.
Targets of therapy include the [[lungs]], [[gastrointestinal tract]] (including [[Insulin]] treatment), the [[reproductive organs]] (including [[Assisted Reproductive Technology]] (ART)) and psychological support.<ref>Davies J et al. Cystic Fibrosis. BMJ. 2007 Dec 15;335(7632):1255–59.</ref>  [[Intravenous therapy|Intravenous]], [[inhalation|inhaled]], and oral antimicrobial agents are used to treat acute and chronic infections. Mechanical devices and inhaled medications are used to alter and clear the thickened mucus. In addition, therapies such as [[gene therapy]] and [[Organ transplantation may also be used in the treatment of cystic fibrosis.


==Medical Therapy==
==Medical Therapy==
[[Antibiotics]] are given whenever pneumonia is suspected or there has been a decline in lung function. Antibiotics are often chosen based on information about prior infections. Many bacteria common in cystic fibrosis are resistant to multiple antibiotics and require weeks of treatment with intravenous antibiotics such as [[vancomycin]], [[tobramycin]], [[meropenem]], [[ciprofloxacin]] and [[piperacillin]]. This prolonged therapy often necessitates hospitalization and insertion of a more permanent [[Intravenous therapy#Peripheral IV lines|IV]] such as a [[Peripherally inserted central catheter|PICC line]] or [[Port-a-Cath]]. Inhaled therapy with antibiotics such as tobramycin and [[colistin]] is often given for months at a time in order to improve lung function by impeding the growth of colonized bacteria.<ref>Pai VB, Nahata MC. ''Efficacy and safety of aerosolized tobramycin in cystic fibrosis.'' Pediatr Pulmonol. 2001 Oct;32(4):314-27. Review. PMID 11568993</ref><ref>Westerman EM, Le Brun PP, Touw DJ, Frijlink HW, Heijerman HG. ''Effect of nebulized colistin sulphate and colistin sulphomethate on lung function in patients with cystic fibrosis: a pilot study.'' J Cyst Fibros. 2004 Mar;3(1):23-8. PMID 15463883</ref> Oral antibiotics such as ciprofloxacin or [[azithromycin]] are sometimes given to help prevent infection or to control ongoing infection.<ref>Hansen CR, Pressler T, Koch C, Hoiby N.''Long-term azithromycin treatment of cystic fibrosis patients with chronic Pseudomonas aeruginosa infection; an observational cohort study.'' J Cyst Fibros. 2005 Mar;4(1):35–40. PMID 15752679</ref> Some individuals spend years between hospitalizations for antibiotics, whereas others require several antibiotic treatments each year.
* Treatment for cystic fibrosis has targeted following consequences of the defect such as [[Gastrointestinal tract|GI]] and pulmonary [[mucus]] plugging and [[infection]].
 
* Medical treatments for patients with cystic fibrosis are include:<ref name="pmid19393104">{{cite journal |vauthors=Ratjen FA |title=Cystic fibrosis: pathogenesis and future treatment strategies |journal=Respir Care |volume=54 |issue=5 |pages=595–605 |year=2009 |pmid=19393104 |doi= |url=}}</ref><ref name="pmid27347364">{{cite journal |vauthors=Edmondson C, Davies JC |title=Current and future treatment options for cystic fibrosis lung disease: latest evidence and clinical implications |journal=Ther Adv Chronic Dis |volume=7 |issue=3 |pages=170–83 |year=2016 |pmid=27347364 |pmc=4907071 |doi=10.1177/2040622316641352 |url=}}</ref><ref name="pmid22093951">{{cite journal |vauthors=Konstan MW, Ratjen F |title=Effect of dornase alfa on inflammation and lung function: potential role in the early treatment of cystic fibrosis |journal=J. Cyst. Fibros. |volume=11 |issue=2 |pages=78–83 |year=2012 |pmid=22093951 |pmc=4090757 |doi=10.1016/j.jcf.2011.10.003 |url=}}</ref>
Several common antibiotics such as tobramycin and vancomycin can cause [[Ototoxicity|hearing loss]] or [[Renal failure|kidney problems]] with long-term use. In order to prevent these [[Adverse drug reaction|side-effect]]s, the amount of antibiotics in the blood are routinely measured and adjusted accordingly.
===Cystic fibrosis===
 
===Antibiotics===
:* 1.'''Pathogen-directed antimicrobial therapy''' <ref name="pmid23540878">{{cite journal| author=Mogayzel PJ, Naureckas ET, Robinson KA, Mueller G, Hadjiliadis D, Hoag JB et al.| title=Cystic fibrosis pulmonary guidelines. Chronic medications for maintenance of lung health. | journal=Am J Respir Crit Care Med | year= 2013 | volume= 187 | issue= 7 | pages= 680-9 | pmid=23540878 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23540878  }} </ref>
::* 1.1 '''Pseudomonas aeruginosa'''
:::* 1.1.1 '''Adults'''
::::* Preferred regimen (1): [[Tobramycin]] 3.3 mg/kg PO tid {{or}} [[Tobramycin]] 12 mg/kg IV q24h {{and}} ([[Piperacillin]] 100 mg/kg PO qid
::::* Preferred regimen (2): [[Ticarcillin]] 100 mg/kg PO qid
::::* Preferred regimen (3): [[Ceftazidime]] 50 mg/kg IV q8h (to maximum of 6 g/day)
::::* Alternative regimen (1): ([[Tobramycin]] 3.3 mg/kg PO tid {{or}} [[Tobramycin]] 12 mg/kg IV q24h) {{and}} [[Aztreonam]] 50 mg/kg IV q8h
::::* Alternative regimen (2): ([[Tobramycin]] 3.3 mg/kg PO tid {{or}} [[Tobramycin]] 12 mg/kg IV q24h) {{and}} [[Imipenem]] 15-25 mg/kg IV q6h
::::* Note: If [[Tobramycin]] resistant add [[Ciprofloxacin]] 500-750 mg PO bid for 7-14 days {{or}} [[Ciprofloxacin]] 400 mg IV q12h for 7-14 days {{or}} [[Levofloxacin]] 750 mg PO qd for 7-14 days
:::* 1.1.2 '''Children'''
::::* Preferred regimen: ([[Ciprofloxacin ]] 500-750 mg PO bid for 7-14 days {{or}} [[Ciprofloxacin ]] 400 mg IV q12h for 7-14 days) {{and}} [[Ceftazidime]] 0.5-1 g IV q8h
::* 1.2 '''Staphylococcus aureus'''
:::* 1.2.1 '''Adults'''
::::* 1.2.1.1 '''Methicillin sensitive staphylococcus aureus'''
:::::* Preferred regimen: [[Nafcillin]] 2 g IV q4h {{or}} [[Oxacillin]] 2 g IV q4h
::::* 1.2.1.2 '''Methicillin resistant staphylococcus aureus'''
:::::* Preferred regimen: [[Vancomycin]] 15-20 mg/kg IV q8-12h {{or}} [[Linezolid]] 600 mg PO/IV q12h
:::* 1.2.2 '''Children'''
::::* 1.2.2.1 '''Methicillin sensitive staphylococcus aureus'''
:::::* Preferred regimen: [[Nafcillin]] 5 mg/kg IV q6h (age > 28 days) {{or}} [[Oxacillin]] 75 mg/kg IV q6h (age > 28 days)
::::* 1.2.2.2 '''Methicillin resistant staphylococcus aureus'''
:::::* Preferred regimen: [[Vancomycin]] 40 mg/kg IV divided q6-8h (age >28 days) {{or}} [[Linezolid]] 10 mg/kg PO/IV q8h (up to age 12)
::* 1.3 '''Burkholderia cepacia'''
:::* Preferred regimen: [[Trimethoprim-sulfamethoxazole]] 5/25 mg/kg IV q6h
:::* Alternative regimen: [[Chloramphenicol]] 15–20 mg/kg PO/IV q6h
 
===Other methods to treat lung disease===
Several mechanical techniques are used to dislodge sputum and encourage its expectoration. In the hospital setting, physical therapy is utilized; a therapist pounds an individual's chest with his or her hands several times a day. Devices that recreate this percussive therapy include the [[ThAIRapy Vest]] and the [[intrapulmonary percussive ventilator]] (IPV). Newer methods such as [[Biphasic Cuirass Ventilation]], and associated clearance mode available in such devices, now integrate a cough assistance phase, as well as a vibration phase for dislodging secretions. [[Biphasic Cuirass Ventilation]] is also shown to provide a bridge to transplantation.  These are portable and adapted for home use.<ref>van der Schans C, Prasad A, Main E. ''Chest physiotherapy compared to no chest physiotherapy for cystic fibrosis.'' Cochrane Database Syst Rev. 2000;(2):CD001401. Review. PMID 10796781</ref> [[Aerobic exercise]] is of great benefit to people with cystic fibrosis. Not only does exercise increase sputum clearance but it also improves cardiovascular and overall health.
 
Aerosolized medications that help loosen secretions include [[dornase alfa]] and [[hypertonic]] [[Saline (medicine)|saline]].<ref>''Kuver R, Lee SP. Hypertonic saline for cystic fibrosis.'' N Engl J Med. 2006 Apr 27;354(17):1848–51; author reply 1848–51. PMID 16642591</ref> Dornase is a [[Recombinant DNA|recombinant]] human [[deoxyribonuclease]], which breaks down DNA in the [[sputum]], thus decreasing its [[viscosity]].<ref>Lieberman J. ''Dornase aerosol effect on sputum viscosity in cases of cystic fibrosis.'' JAMA. 1968 Jul 29;205(5):312-3. PMID 5694947</ref> [[Acetylcysteine|N-Acetylcysteine]] may also decrease sputum viscosity, but research and experience have shown its benefits to be minimal. [[Albuterol]] and [[ipratropium bromide]] are inhaled to increase the size of the small airways by relaxing the surrounding muscles.
 
As lung disease worsens, breathing support from machines may become necessary. Individuals with CF may need to wear special masks at night that help push air into their lungs. These machines, known as [[bilevel positive airway pressure]] (BiPAP) ventilators, help prevent low blood oxygen levels during sleep. BiPAP may also be used during physical therapy to improve sputum clearance.<ref>Moran F, Bradley J. ''Non-invasive ventilation for cystic fibrosis.'' Cochrane Database Syst Rev. 2003;(2):CD002769. Review. PMID 12804435</ref> During severe illness, people with CF may need to have a [[intubation|tube]] placed in their throats and their breathing supported by a ventilator.


===Treatment of other aspects of CF===
* '''1 [[Mucolytic agent|Mucolytics]]'''
[[Image:Icsi.JPG|thumb|200px|left|'''Intracytoplasmic sperm injection''' is used to provide fertility for men with cystic fibrosis.]]
** 1.1 '''Recombinant human deoxyribonuclease I (rhDNase) enzyme'''
Newborns with meconium ileus typically require surgery, whereas adults with [[Anatomical terms of location#Proximal and distal|distal]] intestinal obstruction syndrome typically do not. Treatment of pancreatic insufficiency by replacement of missing digestive enzymes allows the duodenum to properly absorb nutrients and vitamins that would otherwise be lost in the faeces. Even so, most individuals with CF take additional amounts of vitamins [[Vitamin A|A]], [[Vitamin D|D]], [[Vitamin E|E]], and [[Vitamin K|K]] and eat high-calorie meals. It should be noted, however, that nutritional advice given to patients is, at best, mixed: Often, literature encourages the eating of high-fat foods without differentiating between [[saturated fat|saturated]] and [[unsaturated fat]]s/[[trans fat|trans-fats]]; this lack of clear information runs counter to health advice given to the general population, and creates the risk of further serious health problems for people with cystic fibrosis as they grow older. So far, no large-scale research involving the incidence of [[atherosclerosis]] and [[coronary heart disease]] in adults with cystic fibrosis has been conducted. This is likely due to the fact that the vast majority of people with cystic fibrosis do not live long enough to develop clinically significant atherosclerosis or coronary heart disease.
*** Preferred regimen (1): [[Dornase alfa]] 
**: '''Note (1)''': Cleave the [[extracellular]] [[DNA]] and aid [[airway]] clearance.
** 1.2 '''Clevage of [[Disulfide bond|disulfide bonds]] in the [[Mucoprotein|mucoproteins]]'''
*** Preferred regimen (1): [[Acetylcysteine|N-acetyl-L-cysteine]]
**: '''Note (1):''' Also increase levels of the [[intracellular]] [[antioxidant]] [[glutathione]] (GSH) that protect against the [[neutrophil]]-driven tissue damage.
* '''2 [[Airway]] surface [[rehydration]]'''
*:* Preferred regimen (1): [[Hypertonic]] [[Saline (medicine)|saline]]
*:: '''Note (1):''' As it may cause [[bronchoconstriction]], it is commonly used with an [[bronchodilator]].
*:* Preferred regimen (2): Osmotic agents
*:: '''Note (2):''' [[Mannitol]] is a nonabsorbable [[sugar alcohol]] which provides an osmotic gradient on the airway surface
*:* Preferred regimen (3): Correction of [[Ion transporter|ion transport]]


The [[Diabetes mellitus|diabetes]] common to many CF patients is typically treated with [[insulin]] injections or an [[insulin pump]].<ref>Onady GM, Stolfi A. ''Insulin and oral agents for managing cystic fibrosis-related diabetes.'' Cochrane Database Syst Rev. 2005 Jul 20;(3):CD004730. Review. PMID 16034943</ref>  Development of osteoporosis can be prevented by increased intake of vitamin D and [[calcium]], and can be treated by [[bisphosphonate]]s.<ref>Conway SP, Oldroyd B, Morton A, Truscott JG, Peckham DG. ''Effect of oral bisphosphonates on bone mineral density and body composition in adult patients with cystic fibrosis: a pilot study.'' Thorax. 2004 Aug;59(8):699–703. PMID 15282392</ref> Poor growth may be avoided by insertion of a [[feeding tube]] for increasing [[calorie]]s through supplemental feeds or by administration of injected [[growth hormone]].<ref>Hardin DS, Rice J, Ahn C, Ferkol T, Howenstine M, Spears S, Prestidge C, Seilheimer DK, Shepherd R. ''Growth hormone treatment enhances nutrition and growth in children with cystic fibrosis receiving enteral nutrition.''J Pediatr. 2005 Mar;146(3):324-8. PMID 15756212 </ref>
* '''3 [[Anti inflammatory medications|Anti-Inflammatory agents]]'''
*:* Preferred regimen (1): [[Non-steroidal anti-inflammatory drug|Nonsteroidal anti-inflammatory agents (NSAIDs)]]
*:: '''Note (1):''' [[Ibuprofen]] showed some benefit in young patients with mild disease in high [[Dose|doses]].
*:* Preferred regimen (2): Inhaled [[Corticosteroid|corticosteroids]]
*:* Preferred regimen (3): [[Leukotriene B4 receptor|LTB4 receptor]] [[Receptor antagonist|antagonists]]
*:: '''Note (2):''' [[Leukotriene B4|Leukotriene B4 (LTB4)]] is produced by [[Macrophage|macrophages]] and [[Neutrophil|PMNs]] in response to [[infection]] and plays a significant role in inflammatory response.
*:* Preferred regimen (4): [[Azithromycin]]


Sinus infections are treated by prolonged courses of antibiotics. The development of nasal polyps or other chronic changes within the nasal passages may severely limit airflow through the nose. Sinus surgery is often used to alleviate nasal obstruction and to limit further infections. Nasal steroids such as [[fluticasone]] are used to decrease nasal inflammation.<ref>Marks SC, Kissner DG. ''Management of sinusitis in adult cystic fibrosis.'' Am J Rhinol. 1997 Jan-Feb;11(1):11-4. PMID 9065342</ref> Female infertility may be overcome by [[in vitro fertilisation|assisted reproduction]] technology, particularly [[embryo transfer]] techniques. Male infertility may be overcome with [[intracytoplasmic sperm injection]].<ref>Phillipson GT, Petrucco OM, Matthews CD. ''Congenital bilateral absence of the vas deferens, cystic fibrosis mutation analysis and intracytoplasmic sperm injection.'' Hum Reprod. 2000 Feb;15(2):431-5. PMID 10655317</ref> [[Embryo transfer#Third party reproduction|Third party reproduction]] is also a possibility for women with CF.
* '''4 Anti-infective agents'''
** 1.1 '''Prophylaxis'''
*** Preferred regimen (1):  [[Flucloxacillin]]
**: '''Note (1):''' [[Antistaphylococcal penicillins|Anti-staphylococcal antibiotics]] (such as [[flucloxacillin]]) until ~3 years of age is recommended to reduce the [[incidence]] of [[methicillin]]-susceptible [[Staphylococcus aureus|S. aureus]] (MSSA)
** 1.2 '''Eradication of early infection'''
*** Preferred regimen (1):  [[Tobramycin]]
**: '''Note (1):''' If [[Pseudomonas aeruginosa|P. aeruginosa]] not detected and treated aggressively, this [[gram-negative]], [[Opportunistic infection|opportunistic]] bacterium will become [[Chronic (medical)|chronic]].
** 1.3 '''Suppression of chronic infection'''
*** Preferred regimen (1): [[Tobramycin]]
*** Preferred regimen (2):  [[Colistin]]
*** Preferred regimen (3):  [[Aztreonam]]
** 1.4 '''Acute exacerbations'''
**: '''Note (1):''' Pulmonary exacerbations are treated with oral or IV [[Antibiotic|antibiotics]] depending on severity.
* '''5 [[Cystic fibrosis transmembrane conductance regulator|CFTR protein]] defect'''
** 1.1 '''Potentiators'''
*** Preferred regimen (1): [[Ivacaftor]]
**: '''Note (1):''' Enhance the activity of the [[Cystic fibrosis transmembrane conductance regulator|CFTR channel]] if it is correctly located.
**: '''Note (2):''' The most significant advance in the treatment of CF over the last few years has been the development of [[Ivacaftor]] ([[Ivacaftor]] increases the time the [[Cystic fibrosis transmembrane conductance regulator|CFTR channel]] is open)
** 1.2 '''Correctors and combination therapy'''
*** Preferred regimen (1): lumicaftor/[[ivacaftor]]


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}


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Latest revision as of 21:05, 6 April 2018


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

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Overview

Medical treatments for patients with cystic fibrosis has targeted following consequences of the defect such as GI and pulmonary mucus plugging and infection. Treatment include mucolytic agents (dornase alfa, N-acetyl-L-cysteine), airway surface rehydration (hypertonic saline, osmotic agents), anti-infective agents (for prophylaxis, eradication of early infection and suppression of chronic infection), anti-inflammatory agents (NSAIDs, inhaled corticosteroids, LTB4 receptor antagonists and Azithromycin) and potentiators of CFTR protein defect.

Medical Therapy

  • Treatment for cystic fibrosis has targeted following consequences of the defect such as GI and pulmonary mucus plugging and infection.
  • Medical treatments for patients with cystic fibrosis are include:[1][2][3]

Cystic fibrosis

References

  1. ↑ Ratjen FA (2009). "Cystic fibrosis: pathogenesis and future treatment strategies". Respir Care. 54 (5): 595–605. PMID 19393104.
  2. ↑ Edmondson C, Davies JC (2016). "Current and future treatment options for cystic fibrosis lung disease: latest evidence and clinical implications". Ther Adv Chronic Dis. 7 (3): 170–83. doi:10.1177/2040622316641352. PMC 4907071. PMID 27347364.
  3. ↑ Konstan MW, Ratjen F (2012). "Effect of dornase alfa on inflammation and lung function: potential role in the early treatment of cystic fibrosis". J. Cyst. Fibros. 11 (2): 78–83. doi:10.1016/j.jcf.2011.10.003. PMC 4090757. PMID 22093951.
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