​Kembara Xtra - Medicine - Cystic Fibrosis

​Kembara Xtra - Medicine - Cystic Fibrosis 
Cystic fibrosis (CF) is an autosomal recessive genetic disorder that most prominently affects the pulmonary and pancreatic systems but can involve any organ system. As a result of advancements in medical care that have led to a dramatic increase in survival, the number of adults living with CF has surpassed the number of children.


The study of epidemiology, including incidence and prevalence. 

Although it is more prevalent in Caucasians than any other race group, cystic fibrosis is a fatal genetic disease that can affect anyone.
Incidence
1 in 3,200 Caucasians, 1 in 10,000 Latin Americans, 1 in 10,500 Native Americans, 1 in 15,000 African Americans, and 1 in 30,000 Asian Americans are born with cystic fibrosis, respectively, out of the total number of live births in the United States. 
Prevalence

In the United States alone, there are over 30,000 people living with cystic fibrosis, while globally there are 70,000 people affected. Patients diagnosed with cystic fibrosis in the United States had a median expected survival of 46.2 years (95% confidence interval [CI], 45.2–47.6).

Causes and effects: etiology and pathophysiology 

 The primary problem is an aberrant function of an epithelial chloride channel protein. This protein is encoded by the CFTR (CF transmembrane conductance regulator) gene, which is located on band 7q31.2 of the chromosome. CFTR is a regulated chloride channel that affects the activity of chloride and sodium channels on the cell surface. Mutations in CFTR can lead to abnormally viscous secretions that alter organ functions. Obstruction, infection, and inflammation all have a negative effect on lung growth, structure, and function. This can result in decreased mucociliary clearance, intense neutrophilic response with infection, and eventual degradation of supporting tissues, which can lead to bronchiectasis and even eventual death

Genetics CF is a condition that is caused by a single gene and is inherited in an autosomal recessive manner. There are about 1,500 mutations in the CFTR gene, each of which has the potential to cause a different degree of phenotypic CF. The deltaF508 mutation is the most prevalent, accounting for 85.3% of cases in the United States. The G542X mutation accounts for 4.5% of cases, while the G551D mutation accounts for 4.3% of cases. The severity of the condition may also be influenced by other factors, such as modifier genes (such as CFTM1 in the case of meconium ileus), GERD, severe respiratory infections, or environmental factors such as smoke exposure.
GENERAL PREVENTION
Counseling prior to the onset of pregnancy
The American Congress of Obstetricians and Gynecologists advises all North American couples to undergo genetic testing either before conception or during the first and second trimesters of pregnancy.
Patients who are diagnosed with cystic fibrosis before the onset of symptoms have better lung function and nutritional outcomes than those who are recognized after the onset of symptoms. Newborn screening has been a key part of early diagnosis, with 62.4% of new CF cases in 2019 identified using this method.

Conditions That Often Occur Together 

 Diabetes associated to cystic fibrosis (CFRD) – May manifest as a continuous reduction in weight, lung function, or increasing frequency of exacerbations – Leading comorbid consequence (20.7%).
– The consequence of an insulin deficit that gradually worsens – The possibility that early screening and therapy will increase survival rates.
Diseases of the upper respiratory tract — Rhinosinusitis can be found in as many as one hundred percent of people with CF. Up to 86 percent of individuals are found to have nasal polyps.
Pancreatic exocrine insufficiency in the gastrointestinal system (85%–90%)
– Impaired absorption of fatty acids, proteins, and vitamins A, D, E, and K, which are fat-soluble - Hepatobiliary illness, which accounts for 12.6% of cases and includes both cholelithiasis and localized biliary cirrhosis - Meconium ileus at birth (ten to fifteen percent)
- Distal intestinal obstruction syndrome (also known as DIOS), which accounts for 5.3% of cases – GERD (32.7%)

● Endocrine – Bone mineral disease (16.6%)
- Diseases of the Joints (3.0%)
Hypogonadism is characterized by consistently low levels of testosterone in men.
- Menstrual irregularities
Reproductive organs - congenital bilateral absence of the vas deferens with obstructive azoospermia in 98% of males who are affected by this condition. 
● Depression (12.8%)

Things to Think About When Expecting

It's possible that your lung illness will get worse while you're pregnant.
CF has been linked to an increased risk of premature delivery, intrauterine growth restriction, and the need for a cesarean section. However, recent advances in reproductive treatments have made it possible for men with CF to become fathers.
DIAGNOSIS
Diagnostic requirements for cystic fibrosis include the presence of at least one of the following: – Having one or more of the following phenotypic characteristics that are diagnostic of cystic fibrosis: – Chronic pulmonary disease – Chronic sinusitis – Characteristic gastrointestinal and nutritional abnormalities – Salt loss syndromes
○ Obstructive azoospermia
– A history of cystic fibrosis in a sibling; – A positive test for CF in newborns; – PLUS at least one of the following:
– An increased concentration of sweat chloride on two or more occasions – Two mutations that are known to cause cystic fibrosis and are found on distinct alleles
- The presence of abnormalities in nasal potential difference (NPD) testing that are characteristic of cystic fibrosis

Providing an Overview of the Past: During the prenatal period: Routine prenatal ultrasonography reveals hyperechogenic bowel.
If there is evidence of meconium peritonitis, intestinal dilatation, or absence of the gallbladder, the risk is significantly increased.
If these findings are present, a carrier screening for cystic fibrosis should be offered to the parents.

 Past events that occurred during the neonatal period: - Meconium ileus, which accounts for 20% of cases and is typically regarded as diagnostic for CF. - Jaundice that lasts for a long time
Early life and its historical significance: – A failure to thrive – Chronic diarrhea – Anasarca and hypoproteinemia – Pseudotumor cerebri (vitamin A deficiency)
— Hemolytic anemia, which is caused by a lack of vitamin E
Early years of our nation's history: Poor growth, recurrent endobronchial infections, bronchiectasis, chronic pansinusitis, and steatorrhea are all associated with this condition.
– Disseminated intraosseous aspergillosis (DIOS) – Allergic bronchopulmonary aspergillosis (ABPA)
A history of the condition during youth and adulthood (7% of cases diagnosed beyond the age of 18): Suspect with failure to thrive, steatorrhea, and recurrent respiratory problems including: – Recurrent endobronchial infection – Bronchiectasis – ABPA – Chronic sinusitis – Hemoptysis – Pancreatitis – Portal hypertension – Azoospermia – Delayed puberty Suspect with recurrent respiratory problems including: – Bronchiectasis  - Respiratory symptoms that are chronic or persistent, such as airway blockage and infections — Chest x-rays (also known as CXRs) that show persistent infiltrates
- Hypochloremic metabolic acidosis

The Patient's Clinical Examination 
Other symptoms include digital clubbing, growth retardation, and pubertal delay. Respiratory symptoms include rhonchi or crackles, hyperresonance on percussion, and nasal polyps. Gastrointestinal symptoms include hepatosplenomegaly when cirrhosis is present.

Differential Diagnosis Immunologic – Severe combined immunodeficiency Pulmonary – Difficult-to-manage asthma – Chronic obstructive pulmonary disease – Recurrent pneumonia – Chronic/recurrent sinusitis Primary ciliary dyskinesia Gastrointestinal – Celiac disease – Protein-losing enteropathy Pancreatitis of unknown etiology Shwachman-Diamond syndrome GI – Celiac

Results From the Laboratory Initial Examinations (lab, imaging)
During newborn screening, the levels of immunoreactive trypsin (IRT) in the blood are measured.
The sweat test, which is considered the gold standard. 40 mmol/L is considered to be normal.
> >60 mmol/L on at least two separate times indicates possible CF.
CFTR mutation study — Allele-specific PCR identifies more than 90 percent of mutations; there is a small probability of obtaining a false-negative result. The testing of the full sequence takes significantly more time and money.
NPD (in the event that a sweat test and DNA testing produce unclear results) 
● CXR

Additional Assessments, as well as Other Important Factors

In most cases, these tests are requested in order to examine further into the possibility of issues connected to CF: 
Sputum culture to look for common CF pathogens; pulmonary function tests (PFTs); stool elastase and fecal fat after 72 hours; culture of sputum. 
Test of oral glucose tolerance once every year after the age of ten years 
Abnormal sinus CT findings almost always present in a head CT performed on a patient with CF.
Referral to a CF facility during the first 24 to 72 hours of diagnosis is advised (2). Chest CT: after abnormal CXR.[C]
Flexible bronchoscopy with bronchoalveolar lavage is one of the diagnostic procedures and other procedures.

The Cystic Fibrosis Foundation recommends the following for treatment management: – At least one evaluation by a multidisciplinary team, including a dietitian, GI, and social worker each year; – PFT goals of greater than 75% predicted for adults; greater than 100% predicted for children younger than 18 years old. – Four office visits; four respiratory cultures; pulmonary function tests (PFTs) every six months. – Annual screening for ABPA for patients over the age of six years who have a total serum IgE concentration. – Annual vaccine against influenza for all CF patients older than six months. DEXA screening should be performed on all adults and children older than 8 years who have risk factors for osteoporosis.
— Evaluation of one's intake of fat-soluble vitamins on an annual basis in order to rule out vitamin deficiencies Reduce your time spent in environments with high levels of tobacco smoke.
— Vaccination against COVID-19 for all age groups that are eligible
The use of home-based spirometry in conjunction with telehealth is an option worth considering for illness monitoring.
It is recommended that every patient be monitored in a CF center (you may see a list of accredited centers at https://www.cff.org/).
● Infant care:
– Monthly visits for first 6 months of life and then every 2
months until 1 year of life – Fecal elastase testing and
salt supplementation
– Consider palivizumab for RSV prophylaxis in infants with
CF <2 years.

Medication 
The following microorganisms are considered to be causative agents of lung infections: MRSA and MSSA, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, Burkholderia cepacia, and nontuberculous mycobacteria - Antibiotics should be prescribed based on the most likely pathogen, and the majority of antibiotic courses should continue for two weeks.
Infections of the lungs as a whole: - Antibiotics, oral
 Staphylococcus aureus: cephalexin, bactrim (MRSA), or doxycycline (MRSA) Pseudomonas aeruginosa: fluoroquinolones - Antibiotics that are breathed
 Tobi (tobramycin): Nebulize twice daily for 28 days in order to treat P. aeruginosa. After that, cease using it for 28 days, and then start using it again.
Antibiotics used intravenously include colistin, which is utilized more frequently in Europe, and cayston, which is aerosolized aztreonam.
○ S. aureus: cefazolin or nafcillin ○ MRSA: vancomycin or linezolid ○ P. aeruginosa: piperacillin/tazobactam (Zosyn) or ceftazidime plus aminoglycoside (tobramycin) 
The following medications are suggested for long-term usage in the treatment of pulmonary disease: - Recombinant human DNAse (dornase alfa)
- Hypertonic saline (7%)
– Administration of high doses of ibuprofen to patients aged 6 to 17 years old who have a FEV1 that is less than 60 PPV. – Administration of inhaled tobramycin or aztreonam to patients who test positive for P. aeruginosa. - Azithromycin for patients who have been tested positive for P. aeruginosa Ivacaftor and lumacaftor are two CFTR potentiators that were approved in 2015 for use in individuals who have two copies of the F508del mutation in their DNA. 
In the absence of asthma or ABPA, it is not advised that inhalation steroids be used on a long-term basis. There is insufficient evidence to support the long-term use of inhaled -agonist, inhaled anticholinergics, leukotriene modifiers, or inhaled colistin. 
Pancreatic enzymes, which are frequently coupled with H2 blockers or PPI in order to enhance their efficacy 
Cholestasis treatment using ursodeoxycholic acid has not been shown to be beneficial in clinical trials. Supplementation with fat-soluble vitamins (A, D, E, and K).

Extra Medical Intervention 

Aerobic exercise is a helpful addition to the airway clearance approach known as high-frequency chest wall oscillation vest, which is the most popular method for clearing the airways.
Consider bisphosphonate therapy for bone disease caused by cystic fibrosis.

Surgical Procedures The optimal timing for a bilateral lung transplant is dependent on a number of factors.
The following are important criteria for referral: - FEV1 less than 50% of what was expected for patients whose FEV1 was quickly dropping (>20% relative decline within 12 months). – FEV1 projected to be less than 40% with additional indications of decreased mortality – FEV1 predicted to be less than 30% for all other patients
Survival rates after a transplant might reach up to 62% after five years.
Only patients with increasing liver failure, portal hypertension, and gastrointestinal bleeding are candidates for liver transplantation.
Polypectomy of the nose performed in 4.5% of CF patients 

Admissions 

pulmonary exacerbation (the most common reason for hospitalization), bowel obstruction, pancreatitis in patients with appropriate pancreatic function Always admit patients to private rooms and use contact precautions. pulmonary exacerbation is the most common reason for admission.
a cautious use of intravenous fluids in patients whose lung illness is getting worse because of the increased danger of hyponatremia and hypochloremic dehydration brought on by increased salt loss.


After being discharged from the hospital after receiving treatment for a pulmonary exacerbation, you should schedule a follow-up appointment with a CF specialist within two to four weeks.
Regular visits to the clinic every three months, with airway cultures and PFTs when indicated 
● Annual complete nutritional evaluation
DIET A diet heavy in calories and fat, titrated to precise BMI goals set by the Cystic Fibrosis Foundation. If the patient is not meeting their dietary objectives, a referral to a dietician, pancreatic enzymes, or additional tube feeds may be considered.


The progression of lung disease is typically the primary factor in determining how long a person will be able to live after being diagnosed with lung cancer.

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