Addendum: Management of Cystic Fibrosis

Prepared by: Ji Keon LOOI

This is the very informative summary that I promised to upload.

From http://www.childsdoc.org/fall97/cf/fig2.jpg

Below is the discussion on the antibiotics prescribed to Georgia. Only relevant information is included to avoid overloading our meddies with an avalanche of information which might inevitably cause the burnout rate to increase.

Cannot be Emphasised More (Must know-lah)

Pseudomonas aeruginosa is the major culprit in causing complications in patients with cystic fibrosis.

Nice-to-know
Tobramycin

• Tobramycin sulfate is an aminoglycoside antibiotic used to treat various types of bacterial infections, particularly Gram-negative infections.


• Patients with cystic fibrosis will often take an inhalational form (Tobi®) for suppression of Pseudomonas aeruginosa infections. Tobramycin is also combined with dexamethasone as an ophthalmic solution (TobraDex®).

Ticarcillin

• Ticarcillin is a carboxypenicillin. It is almost invariably sold and used in combination with clavulanate as Timentin®.


• Because it is a penicillin, it also falls within the larger class of beta-lactam antibiotics. Its main clinical use is as an injectable antibiotic for the treatment of gram negative bacteria, in particular, Pseudomonas aeruginosa.


• Ticarcillin's antibiotic properties arise from its ability to prevent cross-linking of peptidoglycan during cell wall synthesis when the bacteria tries to divide, causing death.
  

Ciprofloxacin

• Ciprofloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. It functions by inhibiting topoisomerase, an enzyme necessary to separate replicated DNA, thereby inhibiting cell division.
  
• The major adverse effect seen with use is gastrointestinal irritation, common with many antibiotics. Because of its general safety, potency and broad spectrum activity, ciprofloxacin was initially reserved as a drug of last resort for use on difficult and antibiotic-resistant infections.

The information for the above drugs is all derived from http://en.wikipedia.org.

Learning Objectives for PCL 7

Here's a recap on the objectives for this week:

1) Describe the causes and symptoms of cystic fibrosis
2) Understand the process of diagnosing cystic fibrosis
3) Understand the need for multidisciplinary teams in managing this type of chronic illness
4) Review the principles of breaking bad news
5) Understand the difficulties, including family pressures, when managing adolescent patients

Hope this helps. =)

Diagnosing and managing cystic fibrosis in the developing world

This is the link to the summary of the article that talks about the existence of cystic fibrosis in the developing world.

Paediatric Respiratory Reviews, Volume 7, Supplement 1, 2006, Pages S147-S150

Diagnosing and managing cystic fibrosis in the developing world
Sushil K. Kabra, a, , M. Kabraa, S. Shastria and R. Lodhaa aDepartment of Pediatrics, New Delhi 110029, India

The full article is, unfortunately, inaccessible to us. Hope that the summary will be useful.

John

Epidemiology of Cystic Fibrosis

Cystic Fibrosis -the most common autosomal recessive disease for individuals of European
descent
-1 in 2500 newborns are affected with the disease, consequently 1 in 25
individuals are carriers.

• life expectancy -1959 (6 months)
• life expectancy -2006 (38.6 yr)
  -based on data compiled by Cystic Fibrosis Foundation - survival depends largely on the access to health care.
• 1989- the discovery of CF gene
• 1990- scientists successfully made copies of the normal gene, and added them to the CF cells in the laboratory dishes, which corrected the defective cells.
• 1993- the first experimental gene therapy treatment was given to a patient (modified common cold virus was used as carriers or delivery vehicle-carrying the genes to CF cells in the airway)
• the first drug therapy , 1993 =Pulmozyme (mucus-thinning drug) f(x)= improved respiratory infections and lung function.
• 1995, ibuprofen was found to reduce lung inflammation in children with CF, under controlled condition and in high doses.
• in late 1997, tobramycin solution for inhalation=reformulated version of antibiotics which was found to improve lung function and reduce no of hospital stays.
• other treatment strategies to correct the protein product of the gene are currently being tested in clinical trials.
  
• what makes these drugs unique is that the researchers appear to be treating the causes of CF not just the symptoms.
• in Malaysia, approximately 16 patients were diagnosed with CF from 1997 to 2003.

references: Cystic Fibrosis Foundation and National Peadiatric Institute

Respiratory Disorders similar to Cystic Fibrosis

Bronchiectasis

Bronchiectasis is defined as a permanent dilation of bronchi and bronchioles caused by the destruction of the muscle and elastic supporting tissue resulting from or associated with chronic necrotizing infections. It is not a primary disease but one that is secondary to persisting infection or obstruction caused by a variety of conditions, including cystic fibrosis. These include:

1. Bronchial obstruction: common causes include tumours and foreign bodies
2. Congenital or hereditary conditions:
- Cystic Fibrosis: obstruction and infection caused by secretion of abnormally muscid mucus
- Immunodeficiency states (e.g. hypogammaglobulinemia - lack of 1 or more specific antibodies): increased susceptibilty to repeated bacterial infection
3. Childhood pertussis or measles, TB and pneumonia may predispose to bronchiectasis.

Two processes are critical and interwined in the pathogenesis of bronchiectasis: 1. obstruction and 2. chronic persistent infection. Either of these may come first. Normal clearance mechanisms are hampered by obstruction, so secondary infection soon follows. If the obstruction is chronic, the infection persists and causes damage to the bronchial walls, distending the airways permanently; conversely, chronic infection results in obstructive secretions and inflammation throughout the bronchial walls, distending the airway and leading to irreversible dilation.

Clinical Features : -severe, persistent cough
- expectoration of mucopurulent, sometimes fetid (foul smelling), sputum
- sputum may contain flecks of blood
- clubbing may develop
- in widespread bronchiectasis, significant obstructive ventilatory defects occur leading to hypoxemia, hypercapnia, pulmonary hypertension and eventual heart failure (rarely).

Clinical features of common Obstructive Respiratory Diseases

Some of the clinical features of bronchiectasis are similar to other obstructive respiratory diseases, namely asthma, chronic bronchitis and emphysema, and may confuse the physician. Taking a thorough history from the patient (smoker? exposed to air irritants? dyspnea relieved by bronchodilators?) as well as having a good knowledge of the defining features of the common obstructive respiratory diseases will aid in clearing up this confusion and lead to a correct diagnosis.

Now, let us go through the clinical features of common obstructive respiratory diseases.

Asthma:
- severe dyspnea and wheezing during asthmatic attacks
- attacks last from 1 to several hours and subside either spontaneously or with bronchodilators and corticosteroids (obstruction is reversible)
- intervals between attacks are generally free from respiratory defects but there may be persistent, subtle respiratory defects detected by the spirometer.

Classic Emphysema (without chronic bronchitis):
- dyspnea, begins insidiously but is slowly progressive
- hyperventilation
- commonly known as 'pink puffers'
- barrel-chested

Classic Chronic Bronchitis (without emphysema):
- persistent, productive cough for at least 3 consecutive months in at least 2 consecutive years
- production of sputum may persist indefinitely without ventilatory dysfunction
- in severe cases, there may be significant outflow obstruction leading to hypercapnia, hypoxemia and cyanosis

COPD (chronic bronchitis with emphysema):
- features fall somewhere between those found in classic emphysema and classic chronic bronchitis
- gradual development of pulmonary hypertension which may lead to right heart failure, respiratory acidosis, hypoxia, cyanosis and peripheral oedema
- commonly known as 'blue bloaters'

Source: Robins, chapter 13 Basic Pathology, 7th ed

Contributed by John Lee

CAM options for Cystic Fibrosis

By: Chris

Sources:
http://jpepsy.oxfordjournals.org/cgi/content/abstract/24/2/175 Oxford Journals
http://www.umm.edu/altmed/articles/cystic-fibrosis-000045.htm University of Maryland Medical Center

Nutrition and Supplements
Following these nutritional tips may help reduce symptoms:
• Eliminate potential food allergens and foods that increase mucous production, including dairy (milk, cheese, sour cream, and ice cream), wheat (gluten), soy, corn, potatoes, cabbage, bananas, sugar, preservatives, food additives and excessive salt and meats. Your health care provider may want to test for food sensitivities.
• Eat more foods that decrease mucous production, including garlic, onions, watercress, horseradish, mustard, parsley, celery, rose hips tea, pickles, lemon, and anti-inflammatory oils (nuts, seeds, cold-water fish).
• Eat more foods containing digestive enzymes, such as papaya and pineapple.
• Avoid refined foods such as white breads, pastas, and sugar.
• Eat fewer red meats and more lean meats, cold-water fish, tofu (soy, if no allergy) or beans for protein.
• Use healthy cooking oils, such as olive oil or vegetable oil.
• Reduce or eliminate trans-fatty acids, found in commercially baked goods such as cookies, crackers, cakes, French fries, onion rings, donuts, processed foods, and margarine.
• Avoid coffee and other stimulants, alcohol, and tobacco.
• Drink 6 - 8 glasses of filtered water daily.
• Exercise moderately, for 30 minutes daily, 5 days a week.

You may address nutritional deficiencies with the following supplements:
• Omega-3 fatty acids, such as fish oil, 1 - 2 capsules or 1 tablespoonful of oil twice daily, to help decrease inflammation and improve immunity. Cold-water fish, such as salmon or halibut, are good food sources.
• A multivitamin daily, containing the antioxidant vitamins A, C, D, E, the B-vitamins and trace minerals, such as magnesium, calcium, zinc, and selenium.
• Digestive enzymes, 1 - 2 tablets three times daily with meals.
• Coenzyme Q10, 100-200 mg at bedtime, for antioxidant and immune activity.
• N-acetyl cysteine (NAC), 200 mg daily, for antioxidant effects. Alternative health care practitioners may use higher dosages. Check with your health care provider.
• Probiotic supplement (containing Lactobacillus acidophilus) , 5 - 10 billion CFUs (colony forming units) a day, for maintenance of gastrointestinal and immune health. You should refrigerate your acidophilus products.
• Grapefruit seed extract ( Citrus paradisi ), 100 mg capsule or 5 - 10 drops (in favorite beverage) three times daily, for antibacterial or antifungal activity, gastrointestinal health, and immunity.
• Methylsulfonylmethane (MSM), 3,000 mg twice a day, to help decrease inflammation.
• Whey protein, 10 - 20 grams daily mixed in favorite beverage, for support of immunity and weight gain, when needed.


Herbs
Herbs are generally a safe way to strengthen and tone the body's systems. As with any therapy, you should work with your health care provider to get your problem diagnosed before starting any treatment. You may use herbs as dried extracts (capsules, powders, teas), glycerites (glycerine extracts), or tinctures (alcohol extracts). Unless otherwise indicated, you should make teas with 1 tsp. herb per cup of hot water. Steep covered 5 - 10 minutes for leaf or flowers, and 10 - 20 minutes for roots. Drink 2 - 4 cups per day. You may use tinctures alone or in combination as noted.
• Ginkgo ( Ginkgo biloba ) standardized extract, 40 - 80 mg three times daily, for inflammation and as an antioxidant.
• Green tea ( Camellia sinensis ) standardized extract, 250 - 500 mg daily, for antioxidant and immune effects. You may also prepare teas from the leaf of this herb.
• Cat's claw ( Uncaria tomentosa ) standardized extract, 20 mg three times a day, for inflammation, immune and antibacterial or antifungal activity.
• Milk thistle ( Silybum marianum ) seed standardized extract, 80 - 160 mg two to three times daily, for detoxification support.
• Bromelain ( Ananus comosus ) standardized extract, 40 mg three times daily, for pain and inflammation.
• Ground Ivy ( Hedera helix ) standardized extract, 50 mg three times daily, to decrease mucous production and to loosen phlegm.


Homeopathy
Although very few studies have examined the effectiveness of specific homeopathic therapies, professional homeopaths may consider the following treatments to alleviate respiratory symptoms (such as those experienced from cystic fibrosis) based on their knowledge and experience. Before prescribing a remedy, homeopaths take into account a person's constitutional type -- your physical, emotional, and psychological makeup. An experienced homeopath assesses all of these factors when determining the most appropriate treatment for each individual.
The following treatments should be used under the guidance of a licensed, certified homeopath in addition to standard medical care provided by a medical doctor:
• Antimonium tartaricum -- for wet, rattling cough (although the cough is usually too weak to bring up mucus material from the lungs) that is accompanied by extreme fatigue and difficulty breathing. Symptoms usually worsen when the person is lying down.
• Carbo vegetabilis -- for shortness of breath with anxiety, chills, and bluish skin discoloration.


Acupuncture
Acupuncture may alleviate symptoms of cystic fibrosis. Acupuncture may help enhance immune function, normalize digestion, and strengthen respiratory function.


Massage
Therapeutic massage can help drain mucus from the lungs. Parents may reduce anxiety levels by massaging their children with cystic fibrosis and their children may benefit from receiving massage by having less anxiety and improved mood, which in turn may facilitate breathing.

Investigation of Cystic Fibrosis

Chest X ray of Cystic Fibrosis
Sweat Test

• For the past forty plus years, sweat testing has been the most effective, and therefore the most popular, test for detecting cystic fibrosis.

How sweat test is performed

• The sweat test is performed by using an electrode filled with pilocarpine
• A current is run through the electrodes delivering the pilocarpine under the skin.
• The electrodes are removed and the arm is left to rest for about a one-half hour with the filter paper.
• The filter paper will soak up any sweat released from the person's skin. Once the one-half hour is up, the filter paper is placed into a flask and rinsed to release the sweat from the filter.
• A digital chloridometer is used to measure the concentration of chloride ions in the fluid. If more than 60 mmol/liter is detected, cystic fibrosis is diagnosed.

note:The sweat test may not work well in newborns because they do not produce enough sweat. In that case, another type of test, such as the immunoreactive trypsinogen test (IRT), may be used. In the IRT test, blood drawn 2 to 3 days after birth is analyzed for a specific protein called trypsinogen. Positive IRT tests must be confirmed by sweat and other tests.
Heel Prick Test

• is a common procedure for taking a blood sample from the heel of newborn infants.
• Infants with cystic fibrosis 1 to 2 weeks of age show increased levels of immunoreactive trypsin in the plasma in the neonatal heel-prick test.
• The test is positive if immunoreactive trypsin is greater than 80 mcg/litre. It is currently the best screening test for cystic fibrosis but cannot be done after the first few weeks of life since the immunoreactive trypsin falls as pancreatic insufficiency develops.

Genetic Testing

• The diagnosis of cystic fibrosis can also be confirmed by genetic testing in a person who exhibits one or more typical symptoms or has a history of cystic fibrosis in a sibling.
• Finding two abnormal cystic fibrosis genes (mutations) confirms the diagnosis. However, because genetic testing can confirm only a small percentage of the more than 1000 different kinds of cystic fibrosis mutations, failure to detect two mutations does not exclude a diagnosis of cystic fibrosis.
• The disease can be diagnosed prenatally by performing genetic testing on the fetus using chorionic villus sampling or amniocentesis

Pulmonary Function Test

• may show that breathing is compromised and are good indicators of how well the lungs are functioning.
• reduced VC(Vital Capacity) suggest reduce of lung volume (restrictive lung disease),which is present in many patient with CF with advanced lung disease in whom lung parenchyma is destroyed due to chronic lung infection.Strictly speaking, restrictive lung disease may only be diagnosed is TLC(total lung capacity) is reduced
  
• reduced FEV1 suggest narrowing of airway (obstructive lung disease) which is invariably present in patient with CF
  

Chest X-ray & CT Scan

• chest x-rays and computed tomography may be helpful to document lung infection and the extent of lung damage.
• reduced VC(vital capacity) suggest reduction of lung volume (restrictive lung disease),which is present in many patient with CF with advanced lung disease in whom lung parenchyma has been destroyed due to chronic lung infection.Strictly speaking, restrictive lung disease may only be diagnosed if TLC(Total Lung Capacity) is reduced.
• reduced FEV1 also suggest narrowing of airway (obstructive lung disease) which is almost invariably present in patient with CF
  

Characteristic of CF in Chest X-Ray

• Atelectasis

  • Discoid, segmental, lobar with RUL predominance

• Mucoid impaction

  • Nodular and fingerlike densities along bronchovascular bundle

• Cylindrical or cystic bronchiectasis

  • Peribronchial cuffing

• Hilar adenopathy

• Pulmonary arterial hypertension and cor pulmonale

• Recurrent pneumonias, particularly Staph, Pseudomonas and P. cepacia

• Clubbing and hypertrophic osteoarthropathy can occur

• Recurrent pneumothorax is common

Contributed by Lawrence Oh

Sources:
http://pediatrics.about.com/cs/conditions/l/bl_cf.htm
http://www.merck.com/mmhe/sec04/ch053/ch053a.html