Cystic fibrosis - Revision history

Aidan: /* Chronic Management */

2020-07-25T02:07:44Z

Chronic Management

← Older revision		Revision as of 02:07, 25 July 2020
Line 54:		Line 54:
	*Diagnostic tests including 2x CF mutations, or 2x positive sweat chloride test		*Diagnostic tests including 2x CF mutations, or 2x positive sweat chloride test

	==~~Chronic~~ Management==		==Management==

			=== Chronic Management ===

	*Overall goals are to preserve lung function by decreasing infection, inflammation, and mucous production		*Overall goals are to preserve lung function by decreasing infection, inflammation, and mucous production
Line 77:		Line 79:
	**For G551D (3% of cases) (a class III defect in gating), ivacaftor (VX700) is an experimental agent that causes an absolute increase in FEV1 by 10%		**For G551D (3% of cases) (a class III defect in gating), ivacaftor (VX700) is an experimental agent that causes an absolute increase in FEV1 by 10%

	==Acute Management==		===Acute Management===

	*See [[Cystic fibrosis pulmonary exacerbation]]		*See [[Cystic fibrosis pulmonary exacerbation]]

Aidan: /* Microbiology */

2020-07-25T01:32:31Z

Microbiology

← Older revision		Revision as of 01:32, 25 July 2020
Line 22:		Line 22:
	*By young adulthood, ''Pseudomonas'' followed by ''[[Staphylococcus aureus]]'' are most common		*By young adulthood, ''Pseudomonas'' followed by ''[[Staphylococcus aureus]]'' are most common
	*Others include ''[[Aspergillus species\|Aspergillus]]'', ''[[Stenotrophomonas maltophilia]]'', ''[[Burkholderia cepacia]]'', and [[MRSA]]		*Others include ''[[Aspergillus species\|Aspergillus]]'', ''[[Stenotrophomonas maltophilia]]'', ''[[Burkholderia cepacia]]'', and [[MRSA]]
			*[[Non-tuberculous mycobacteria]] are also involved, especially [[Mycobacterium abscessus]] and [[Mycobacterium avium complex]]

	===Epidemiology===		===Epidemiology===

Aidan: /* Microbiology */ linkified

2020-07-25T01:05:30Z

Microbiology: linkified

Show changes

Aidan: Text replacement - "Clinical Presentation" to "Clinical Manifestations"

2020-07-14T23:18:56Z

Text replacement - "Clinical Presentation" to "Clinical Manifestations"

← Older revision		Revision as of 23:18, 14 July 2020
Line 29:		Line 29:
	* 1:25 carriers		* 1:25 carriers

	== Clinical ~~Presentation~~ ==		== Clinical Manifestations ==

	* On newborn screening, with increased serum trypsinogen (take top 2% and sequence for most common mutations)		* On newborn screening, with increased serum trypsinogen (take top 2% and sequence for most common mutations)

Maintenance script: Imported from text file

2020-07-04T01:17:30Z

Imported from text file

New page

* Autosomal recessive disease caused by missions in CFTR that causes a syndrome of respiratory disease, pancreatic insufficiency, constipation, and other disorders arising from the increased thickness of mucous production

== Background ==

=== Pathophysiology ===

* Caused by mutations in the CFTR gene which encodes the cystic fibrosis transmembrane conductance regulator, a cAMP-regulated chloride channel
* CFTR is present in epithelial cells lining the airways, biliary tree, intestines, vas deferens, sweat ducts, and pancreatic ducts >2000 possible defects, causing a wide range of presentations
* Most common is delta-F508 (which falls into classes II, III, and VI)
* Classified into:
** Normal
** I: no synthesis (e.g. a nonsense or frameshift mutation)
** II: blocked processing or folding
** III: blocked regulation or a gating problem
** IV: altered conductance
** V: reduced synthesis
** VI: unstable and quickly degraded

=== Microbiology ===

* In childhood, ''Staph. aureus'' and ''Haemophilus influenza'' are most common
* By young adulthood, ''Pseudomonas'' followed by ''Staph. aureus'' are most common
* Others include ''Aspergillus'', ''Stenotrophomonas maltophila'', ''Burkholderia cepacia'', and MRSA

=== Epidemiology ===

* Autosomal recessive disease
* 1:3300 Caucasians
* 1:25 carriers

== Clinical Presentation ==

* On newborn screening, with increased serum trypsinogen (take top 2% and sequence for most common mutations)

== Differential Diagnosis ==
* For positive sweat chloride test:
** Untreated Addison disease
** Ectodermal dysplasia
** Some glycogen storage diseases
** Untreated hypothyroidism
** Adulthood

== Investigations ==

* Sweat chloride concentration greater than 60 mEq/L (or 90 mEq/L for adults) with an appropriate clinical context or family history
* Genotyping

== Diagnosis ==

* Must have both clinical features and positive diagnostic testing
* Clinical features include cystic fibrosis, family history, or positive newborn screen
* Diagnostic tests including 2x CF mutations, or 2x positive sweat chloride test

== Chronic Management ==

* Overall goals are to preserve lung function by decreasing infection, inflammation, and mucous production
* Chronic *Pseudomonas *infection defined as >50% of cultures positive for ''Pseudomonas'' in the past 12 months
* Vaccinations
* Decrease mucous burden with mucolytics (hypertonic saline or Pulmozyme)
** Chronic productive cough or FEV1 < 90%, start mucolytic
** Mild lung disease, no daily cough, and FEV1 >90%, physician and patient decision
** When starting, needs a trial of mucolytics with before-and-after PFTs to ensure no bronchospasm
* Decrease bacterial burden with inhaled antibiotics (tobramycin, aztreonam)
** Chronic growth of ''Pseudomonas'', chronically suppress
** New growth of ''Pseudomonas'', attempt to eradicate with short course
** ''B. cepacia'' complex, physician decision
** ''Stenotrophomonas maltophilia'', physician decision
** ''Achromobacter xyloxidans'', physician decision
* Decrease inflammation with chronic oral azithromycin
** Chronic growth of ''Pseudomonas'', treat if no Mycobacteria
** ''B. cepacia'' complex, no guidelines
** ''Staph aureus'', H. influenzae, physician decision (small benefit)
** Rule out non-tuberculous mycobacteria first
* Targeted therapies
** For G551D (3% of cases) (a class III defect in gating), ivacaftor (VX700) is an experimental agent that causes an absolute increase in FEV1 by 10%

== Acute Management ==

* See [[Cystic fibrosis pulmonary exacerbation]]
* See [[Cystic fibrosis antibiotic dosing]]

== Prognosis ==

* FEV1 is main predictor of survival
* FEV1 starts declining after Pseudomonas colonization
* Survival decreases with increasing pulmonary exacerbations
** 25% fail to recover to 90% of baseline FEV1
** 40% fail to recover to 100% of baseline FEV1
* Life expectancy is 1 year once FEV1 drops to 20% of predicted

[[Category:Pediatrics]]
[[Category:Respirology]]