The Cystic Fibrosis Foundation and the Stanford CF Center staff recommend the following sequence for inhaled medications:

• Bronchodilators (Albuterol, Combivent™, Xopenex™) to open the airways
• Hypertonic Saline (7%) to mobilize mucus and improve airway clearance
• Pulmozyme™ (DNAse) to thin mucus
• *Airway Clearance Technique: Vest, Flutter™, Chest PT, IPV, etc.
• Antibiotics (TOBI™, Colistin, Cayston). The previous therapies open and clear the airways of mucus, allowing these antibiotics to work on remaining bacteria.
• Steroids (Flovent™, Pulmicort™, QVAR™)

* When using the Vest for airway clearance, make sure there is aerosol delivery during the entire vest session.

If you start coughing blood, temporarily stop Pulmozine™, saline, airway clearance technique, and inhaled antibiotics. Call your CF doctor or nurse for further advice.

With a respiratory illness or change in symptoms:

• Begin or increase airway clearance techniques.
• Use breathing treatments as ordered; you can use bronchodilators every three to four hours, and often additional Vest and/or hypertonic saline treatments are useful.
• Contact your CF doctor or nurse to see if antibiotics or additional intervention is needed.

The CF Center at Stanford has an infection control policy that seeks to reduce the risks to people with CF from potential cross infection. We strive actively to protect our patients by following the guidelines set out by CFF in their consensus statement on infection control.

The articles on this page describe general aspects of lung infections, the meaning of bacterial resistance, and what an allergic reaction to a CF drug really means.

Cystic Fibrosis Lung Infections and Infection Control
by Jane L. Burns, M.D.

Cystic fibrosis lung infections

• What organisms cause lung infections in CF?
• Which ones can be spread from person to person?
• How can we prevent that spread?

Know Your Bugs

• Viruses
• Bacteria
• Fungus

Viruses

• Cause colds and flu
  • Rhinovirus
  • RSV
  • Parainfluenza
  • Influenza
• Can trigger CF exacerbation, hospitalization
• Commonly spread from person to person whether with CF or without CF

Pseudomonas aeruginosa

• Most common cause of lung infection in CF
• Is associated with worsening lung disease, especially "mucoid"
• Is getting more resistant to antibiotics
• Usually not spread from person to person,
• Rarely "bad bugs" are spread in CF

Burkholderia cepacia complex

• Rare in CF (less than 5% of patients)
• Can cause severe disease in about 25%
  • Sometimes, patients have no ill effects
  • Severe infections probably dependent on species of B. cepacia
• Naturally very resistant to antibiotics
• Frequently spread from person to person, especially "bad bugs"

Staphylococcus aureus

• Usually the first bacteria seen in young children with CF
• Can cause serious infections in healthy people
• Increasingly resistant to the usual antibiotics
• Can be carried even by healthy people and spread from person to person (CF and non-CF)

Haemophilus influenzae (H. flu)

• Same bacteria that can cause ear and sinus infections in non-CF children
• Hib vaccine prevents serious infections
• No effect of the vaccine in CF, the CF bug is not prevented by the vaccine
• Usually responsive to antibiotics

Other Bacteria

• Emerging, antibiotic resistant bacteria:
  • Stenotrophomonas maltophilia
  • Achromobacter xylosoxidans
• Seem to emerge with aggressive antibiotic treatment
• Probably not as problematic in CF as Pseudomonas and B. cepacia
• Not as easily spread as B. cepacia, Staph.

Non-tuberculous mycobacteria

• Relatives of TB (tuberculosis), but not nearly as dangerous to healthy people
• Some CF patients have problems with them, in others, harmless
• Require long treatment, multiple antibiotics
• Not spread from person to person

Aspergillus

• Can cause allergic problems, wheezing
  • Allergic bronchopulmonary aspergillosis (ABPA)
  • Can be treated with antifungal agents, steroids
• Can cause severe infections after transplant
• Other fungi rarely cause infections
• Comes from the environment, not spread from person to person

How  are  germs  spread?

• Droplet
  • Coughing, sneezing, talking
  • Can only go about 3 feet through the air
  • Viruses and a few bacteria can be spread this way
• Direct contact
  • Kissing, shaking hands
  • Viruses and bacteria can be spread this way
• Indirect contact
  • Shared eating utensils, respiratory therapy equipment, soiled tissues
  • Viruses and bacteria can be spread this way

PREVENTION

• Know your own bugs
• Recognize that things may have changed since your last culture
• Recognize that other CF patients may not know their bugs
• Comply with infection control recommendations to protect yourself and others

CFF Consensus conference on Infection Control

• Meeting in May 2001, Bethesda MD
• CF doctors, microbiologists, nurses, respiratory therapists, ethicists, lawyers, and CF patients all represented
• Doctors from Europe and Canada also there
• Tried to come to a consensus on the safest measures that will have the least effect on patients lives

Standard Precautions

• Recommendations from the CDC and HICPAC for all patients to prevent spread
• Hand hygiene (always!)
• Gloves when risk of direct or indirect contact
• Gowns to prevent soiling of clothes with contact or droplets
• Masks to prevent contamination of mucous membranes (eyes, nose, mouth) with droplets

To summarize…

• Know your bugs!
• Wash your hands!
• Become educated about how to protect yourself and others

Bacterial Resistance and Infection Control
by Richard Moss, M.D.

Many patients and families are concerned about infection control and the measures taken at our CF Center to reduce the risk of transmission of resistant bacteria while continuing to foster a sense of community and support. Here are some relevant facts which may help explain our policies and procedures.

First, it is essential to understand what we mean when we talk about resistance of bacteria to antibiotics. What does it really mean?

There are 4 categories of bacterial sensitivity to antibiotics:

• First, pansensitive - this means the bug is sensitive to all the antibiotics usually tested for potential treatment.
• Second, sensitive - the bug is sensitive to several potential antibiotics, but it may be resistant to others.
• Third, multiresistant - this is more complicated. According to the current definition, this means the bug is resistant to all antibiotics in two or more classes of antibiotics. Currently 3 classes of antibiotics are considered appropriate for treatment of Pseudomonas: certain beta-lactams, such as ceftazidime (Fortaz®); certain quinolones, such as ciprofloxacin (Cipro®); and aminoglycosides, such as tobramycin (Nebcin®, Tobi®).
• Fourth, panresistant - the bug is resistant to all tested antibiotics of all classes.

CASE STUDY

Here is an example of an antibiotic sensitivity report for fictional patient Jane Smith on a clinic visit expectorated sputum culture that grew three strains of Pseudomonas aeruginosa, one strain of Stenotrophomonas maltophilia, and Staphylococcus aureus. What is listed is the antibiotic sensitivity pattern for 1 of the 3 strains of Pseudomonas, i.e., just one of 5 lists of antibiotic sensitivities we would get from this single culture report on this patient on this day:

What is your categorization of this bug, and how should Jane Smith be approached regarding infection control on a clinic visit? You wouldn't be expected to know the answer without a lot more knowledge of how the tests are done and what they mean. Here are several points about this culture result:

• This bug is multiresistant. This is because it is resistant to all tested antibiotics in 2 out of the three 3 represented.
  1. The only quinolone tested (because it has the highest and only frequently present quinolone activity against Pseudomonas) is ciprofloxacin. Resistant.
  2. The three aminoglycosides tested are gentamicin, tobramycin, and amikacin. Resistant to all three.
  3. The rest of the drugs shown--total of 7--are beta-lactams. Of these 7 drugs, the bug is sensitive to just one, cefepime. This sensitivity keeps the bug from being called panresistant. But because it is multiresistant Jane will be asked to don a mask for her clinic visit, and if hospitalized she will have respiratory isolation procedures in place.
• Because it is multiresistant does it mean Jane is untreatable? No! If she is sick we can start cefepime (an iv-only drug). We would probably combine that with iv tobramycin, because even though the report says she is resistant to tobramycin there is synergy between these two antibiotic classes in attacking Pseudomonas.
• If Jane is a little sick, or her PFTs have dropped, we may put her on Tobi®. Why? Although the conventional test (Kirby Bauer disc diffusion) says her bug is resistant to tobramycin, the "E test" done at Stanford (not commonly done elsewhere) shows the bug can be killed by tobramycin if a concentration of 32 micrograms per milliliter [mcg/ml] can be achieved. It is difficult to do this by iv tobramycin without risking toxicity to kidneys or inner ear, but it is easy to do by having Jane inhale 300 milligrams of tobramcyin solution for inhalation-a Tobi® dose -- twice daily. This will produce a sputum level in the neighborhood of 1,000 mcg/ml, far above that needed to kill the bug, even after allowing for the fact that tobramycin can lose up to 90% of its activity in CF sputum.

THE CONCEPT OF RESISTANCE - A RED HERRING IN CF?

We have problems even defining and understanding what resistance means in the world of CF. The word resistance refers to lab tests done in a liquid suspension with a conventional set "dose" of bacteria and cutoffs between "sensitive" and "resistant" refer to levels of that antibiotic traditionally associated with curing systemic (i.e, blood) infections.

We know in CF that the conventional term "resistance" is questionable clinically. For example, if your Pseudomonas is called "resistant" because tobramycin does not kill it at the conventional testing cutoff level of 8 mcg/ml, this is not very relevant in a disease where the bug is living in the mucus rather than tissue or blood, and we can deliver 1,000 mcg/ml Tobi® to the mucus by aerosol. Moreover, the way the bug lives in your lung is as a mucoid biofilm-a gigantic communal mass of bacteria (up to one billion bacteria in one gram of sputum!) stuck together by a slimy material called alginate or mucoid exopolysaccharide. This is much different than the way lab antibiotic testing is done with individual bugs swimming around freely in liquid suspension.

INFECTION CONTROL

We rely on universal direct and indirect contact precautions for ALL patients to reduce transmission of bacteria. The simplest way to describe this is to imagine a three foot zone around your body that should ideally not be entered by another patient (unless you live with them), and no shared object use without proper cleaning in between. All contacts by caregivers should be preceded by handwashing and cleaning of multi-use instruments such as stethoscopes.

We are concerned about acquisition and spread of Pseudomonas, and the infection control measures are designed to reduce the chance of spread. For multiresistant and panresistant bugs, we add restrictions on the patient such as use of mask when coming to clinic, and isolation when hospitalized. This is done to reduce the chance of transmission, not because the patient is sicker! The mask is an additional level of precaution but contact precautions are the key element for ALL patients.

In the near future the CFF Consensus Conference report on Infection Control will be published and available for detailed reading.

REPORTING CULTURE RESULTS TO PATIENTS

Ideally, we would like to track levels of resistance in all cultures and inform all patients promptly. In practice, this is a very difficult task. In our center we see over 200 patients a year, on average 4 times, yielding at least 800 "surveillance" bacterial cultures alone. Add to this cultures obtained when the patient is sick, and when hospitalized. Each specimen may contain multiple bacterial strains that are each tested for antibiotic sensitivities. And this is just for bacteria; often further cultures are also obtained for molds, mycobacteria, and so on. Finally, many other tests (bloodwork, x-rays, PFTs) are also being monitored.

Given our staff resources we have in the past focused on the priority of promptly informing people who are culture negative for Pseudomonas when they pick up Pseudomonas because we want to try to eradicate it early. Later on this becomes impossible, so that most people who have years of carrying mucoid Pseudomonas cannot achieve eradication by any known treatment. We do not routinely inform patients of each culture result in that instance. Besides the impracticality of the numbers, we know that typically a strain may go from "resistant" to "sensitive" and back and forth over time, confusing many people and raising needless anxiety. Instead, we focus on dealing with the situation at each clinic visit as well as of course during hospitalizations.

The infection control guidelines currently being prepared for publication do not distinguish between patients with sensitive or resistant Pseudomonas outside health care settings, but rather recommend a uniform set of infection control behaviors for all persons with CF. Thus, we have no specific reason to routinely inform patients with long-term Pseudomonas carriage of culture-to-culture changes in their resistance pattern with regard to their outside the health care system interactions, but urge adherence to the general recommendations. Cultures are checked before the next clinic visit so we can institute appropriate infection control for that visit.

Recently, our staff met and decided to go beyond current standard practice and monitor sensitivity results for long-term Pseudomonas patients, and send a letter out informing patients with resistant organisms of the mask requirement for clinic. We hope this system minimizes surprises about our infection control measures in the clinic and hospital. It is critical to remember that a "resistant" bug report does not and should not be taken as a bad thing in and of itself, and that our main interest as to timing use of this information focuses on our health-care facility setting, and early monitoring of new Pseudomonas. Now, in addition, we will attempt to track long-term carriers and provide "early warning" infection control letters.

CF Drug Allergies
by Richard Moss, M.D.

Antibiotics are essential part of treatment for cystic fibrosis lung disease. Most patients receive numerous courses of oral, iv or inhaled antibiotics for symptoms and many patients are maintained on long-term "suppressive" regimes of oral or inhaled antibiotics. It is not surprising that given this enormous exposure a substantial problem with allergic reactions exists. Most reactions and reports of sensitization have been to the class of antibiotics derived from penicillin that are effective against Pseudomonas aeruginosa, the major bacterial infection in CF. These are called anti-pseudomonal b-lactam antibiotics [BLA]. Allergy to aminoglycosides such as tobramcyin and quinolones such as ciprofloxacin are very rare.

A general principle of allergy is that reactions are more likely the more closely related two molecules are. Within the BLA family, there are 4 subfamilies chemically related by a core structure called the b-lactam nucleus but quite different in their side chains. The BLA subfamilies and the drugs used in CF are as follows:

1. Penicillins
   • Carboxypenicillins
     Ticarcillin (Ticar, Timentin)
   • Acylaminopenicillins
     Piperacillin (Pipracil, Zosyn)
2. Carbapenems
   • Imipenem (Primaxin)
   • Meropenem (Merrem)
3. Monbactams
   • Aztreonam (Azactam)
4. Cephalosporins
   • Ceftazidime (Fortaz, Tazicef)
   • Cefepime (Maxipime)

It turns out that most BLA allergic reactions occur due to allergic or IgE antibodies being formed against the side chains, so most reactions occur upon re-exposure to the same drug, or to a closely related drug in the same subfamily with a similar side chain structure. The chances of a reaction diminish as the structure becomes more dissimilar.

Allergic reactions to BLA occur in 1-10% of subjects during a given course of treatment, with the variation in incidence dependent upon several factors such as the subject population, drugs involved, and ascertainment methods. The vast majority of these are limited to skin or underlying tissues, with only 2-10% involving life-threatening respiratory or cardiovascular reactions. Up to 9% of the life-threatening reactions may result in death, yielding a final fatality rate estimated at about 1 in 50,000 treatment courses.

Most of the information in the medical literature is based on allergy to penicillin itself, not the many derivatives such as those used against Pseudomonas. Ten to 73% of patients giving a history of penicillin allergy react on allergy skin testing to penicillin-derived chemicals or reagents, depending upon time elapsed since the reaction, nature of the reaction, age of subject, and other factors. Evaluation of penicillin allergy with just two commercially available reagents, penicillin and its major metabolite penicilloyl-polylysine [Pre-Pen®], detects 65-93% of allergic individuals. The remainder of allergic subjects are reactive only to minor penicillin metabolites which are unstable and not commercially available. Unfortunately, those sensitized to these minor metabolites are at higher risk of more serious reactions if re-exposed to penicillin.

For people sensitized to BLAs other than penicillin, skin testing and prediction of subsequent clinical reactivity becomes much more difficult. Major and minor metabolites of these drugs are not commercially available and are not well characterized. Cross-reaction studies between various BLAs yield varying results and clinical responses are not predictable from skin test responses. Thus, the safest course is usually to avoid BLAs and choose an alternate class of drug when possible. However, treatment of Pseudomonas aeruginosa infection rarely offers this choice; usually, a BLA is essential.

Studies of BLA allergy in CF have been reported since 1970, including a number studies from our CF Center over the last 15 years. In general, these show BLA allergy rates of about 15-25% in CF patients and 5-10% of iv BLA treatment courses. These reactions are usually in-hospital, physician-observed, well-characterized and documented. Reactions are usually seen in older patients with multiple prior exposures. Reactions always include the skin (itching, redness, hives, swelling) while respiratory involvement occurs in only a small minority. However these can be quite severe with bronchospasm or largyngeal edema. Cardiovascular problems are very rare.

Unusual cases of patients with reactions to several classes of antibiotics, not just BLA, have been reported also.

Our studies using skin testing and laboratory immunological assays suggest that BLA allergy in CF is mainly drug-specific. This situation differs from other penicillin allergic patients in the literature, whose allergy appears mainly directed to the core BLA nucleus. It is clear that cross-reactivity between various BLA occurs, and that any BLA may cause an allergic reaction. It is not currently possible to predict which CF patients will become sensitized, although multiple courses, high doses, and the intravenous route of drug exposure are key elements in sensitization. Patients may become sensitized during or between any given course of antibiotic therapy.

Treatment

The main treatment strategy in CF is called desensitization. Desensitization is the administration of gradually increasing doses of a drug under close observation for adverse effects. Desensitization has been performed safely in pregnant women, critically ill patients, and patients with serious but not life-threatening infections. How desensitization works is incompletely understood.

Desensitization may be performed orally with oral drugs, but most BLA used in CF are given only by the iv route, so most desensitization procedures are done intravenously. In addition, only the iv route allows control of the dose and rapidity by which the drug enters the bloodstream. During iv desensitization, the earliest signs of a reaction can be at least in part immediately managed by slowing or stopping the infusion. If the reaction history was severe pretreatment with Benadryl and sometimes steroids may be included. We have performed many hundreds of iv desensitization for BLA allergy in CF since 1983. Skin rashes occur in 25-30% of cases, often during or just after the last and highest dose. Mild reactions are treated with slowed infusion rates and iv Benadryl. More serious reactions occur in 1-2% of cases and require immediate management and discontinuation of desensitization. In virtually all of these cases, iv desensitization with another BLA has been successfully performed 1-2 days after the patient has been stabilized. Desensitization relies on staying on the prescribed drug schedule; missed doses increase the possibility of a reaction.

While it is possible to maintain desensitization by indefinitely staying on the drug in question, in most cases this is impractical in CF. Instead, we rely on history (identifying prior drug reactions) and repeat desensitization if a BLA causing a reaction needs to be given again. In many instances, an alternative BLA can be chosen instead. Studies show the likelihood of a cross-reactive allergic reaction is in the range of 2-5% if a different BLA subfamily drug is used (e.g., you reacted to piperacillin and we then use ceftazidime). Often in this situation we will give a test dose (1/10 or 1/100 of the full dose) first, and then the full dose if no symptoms occur.

Delayed reactions. Delayed reactions take days or weeks to occur and are not life-threatening, but can be quite troubling. They usually consist of fever, malaise, muscle aches, non-itchy flat irregular red rashes, and sore sometimes swollen joints. Rarely enlarged glands or internal organs, or more severe skin rashes may occur. Delayed reactions are more common with piperacillin than other BLAs. Besides stopping the drug, steroids are often given. Desensitization does not prevent delayed reactions if the same drug is given again.

What You Can Do

Know your drug allergy history! Record the name of the drug, when the reaction occurred and what happened. Do NOT assume the medical record is foolproof - it is not! YOU should take charge of your medical history and make sure you are not exposed to a BLA you reacted to in the past without proper evaluation and a plan.

Nutrition and CF

Good nutrition for a child or adult with CF means more than just eating a balanced, normal diet. A high-calorie diet containing all the essential nutrients without restriction on fat intake is recommended, along with pancreatic enzymes to control digestive symptoms, and supplemental fat-soluble vitamins: A, D, E, and K. To maintain weight, frequent and high-calorie meals and snacks are recommended.

What is a " good diet " for someone with CF?
Nutritional requirements for each person with CF are unique; there is no universal recommendation that applies to everyone. Requirements and recommendations depend on many factors including age, gender, severity of lung disease, malabsorption and the type of food a person likes. But there are some general recommendations for anyone with CF:

More Calories
Most people with CF have a higher caloric requirement than other individuals of the same age and sex because:

• More energy is used in breathing.
• Extra energy is used in fighting infections and during fevers.
• Fewer of the energy-producing nutrients in food are properly digested and absorbed into the body, even when treatment is optimal.

Research has shown that good nutrition is important for pulmonary function, and can contribute to a longer life expectancy.

Vitamins
Vitamins A,D, E, and K are known as the fat-soluble vitamins. These vitamins require an adequate amount of fat to be absorbed properly. Because people with CF can have problems with absorption of fat, it is important to replace these vitamins.

Pancreatic Enzymes
CF causes production of a thick mucus that plugs the duct leading from the pancreas to the small intestine. Consequently, the enzymes produced by the pancreas to help digest food cannot move into the small intestine. If left untreated, one result is malabsorption, an inability to properly absorb nutrients. To compensate for this enzyme shortage, many people with CF must take replacement pancreatic enzymes.

When Do I Take Enzymes?
Enzymes must be taken to help digest every meal and snack, except for snacks that are virtually free of protein, starch, and fat (such as apple juice). Studies show that enzyme preparations are equally effective when taken anywhere from a half-hour before to a half-hour after eating. That way, the enzymes are in the small intestine when needed.

What If I Can't Eat Enough Calories?
Some people with CF cannot take in enough calories by mouth to gain or maintain weight. For them, calories and all the essential nutrients can be given by tube feedings. Many achieve excellent nutrition through this method.

Is There Any Help With Nutritional Products?
The Scandipharm Comprehensive Care Program for CFTM provides free ADEKs® multivitamins, Scandishake® nutritional supplements, and Flutter® mucus-clearance devices to people taking Ultrase®. The program enhances Scandipharm's mission of improving the overall quality of care, while lowering its cost. For more information on this program, talk to one of the CF team members.

How Can I Manage CF and Nutrition?
The key to managing nutritional needs successfully is to match dietary needs to each individual:

• Assess individual needs
• Adjust for clinical status
• Factor in age-related needs

A comprehensive nutritional management plan developed jointly by the CF Team, the person with CF, and the family is needed.

Pulmonary Function Tests

What are Pulmonary Function Tests (PFTs)?
Pulmonary function tests are machine assessments of the performance of the lungs, measuring basic function and volume. Many of the tests are done in a special Pulmonary Function Laboratory. There are various computerized machines that answer very specific questions about lung function.

Some Common Tests:
Spirometry: tests done at every clinic visit to determine the vital capacity of the lungs. Spirometry measures the amount of air breathed and the speed at which it is blown out.

• SVC: (slow vital capacity)
• FVC: (forced vital capacity) This measures the volume of air that is blown out in a single maximum exhaled breath. It is inversely related to the amount of air trapped by obstruction. The worse the airway obstruction, the less the FVC.
• FeV1: (forced expiratory volume) This measures how fast the lungs can push air out in one second. Your result is measured against a predicted result, a mean of values in healthy people of the same sex, height, and weight. The result is written as the percent of the predicted result. The less air expired in the first second, the higher the level of airway obstruction.

Lung Volume Measurements: these indicate the size of the lungs and the amount of air remaining inside after exhalation

Exercise testing: Problems may become more apparent during exercise, therefore, sometimes PFTs are measured during treadmill or other exercise while heart and respiratory rates are monitored.

Blood oxygenation measures(ABGs): These indicate how effective the lungs are in bringing oxygen into the bloodstream and removing carbon dioxide from it.

What do these tests show in my lungs?

• How well my lungs are working
• If antibiotics are helping to clear up an infection
• If the current daily care program is adequate

How often should they be done?

• Spirometry is initiated at 5 or 6 years of age or whenever a child can understand the instructions and cooperate. After that, spirometry is done at every clinic visit so that the clinician can evaluate your progress. Research is being done on methods to measure infants.
• Full PFTs are done on an annual basis. They are extremely accurate monitors of change in lung function, even when no new symptoms or signs have emerged.

How some of the spirometry tests are done:
A spirometer is a tube leading into a pneumotach which measures air flow and volume. The results are graphed and displayed on the computer monitor. In order to make accurate measurements, nose plugs are worn to close the nasal passages so that the air can only be blown out through the mouth.

• FVC: (forced vital capacity) After several slow deep breaths in, you breathe out as hard as you can for six full seconds. This measures the volume of air that is blown out in a single maximum exhaled breath.
• FeV1: (forced expiratory volume) After several slow deep breaths in, you blast all of the air out of your lungs as fast as possible in one long burst. This measures how fast the lungs can push air out in one second.

Metered Dose Inhaler

What is a Metered Dose Inhaler (MDI)?

An MDI is device that sends a measured amount of medicine directly into the lungs. Sometimes it is used with a spacer to make it easier to use. The spacer can help to deliver the medicine to the lungs and lessen the bad taste of the medicine.

How do I use an MDI?

1. Remove the cap and hold the inhaler upright.
2. Place the spacer, if used, on the inhaler.
3. Shake the inhaler.
4. Tilt your head back a bit. Breathe in and breathe out. Then place the spacer or mouthpiece in your mouth.
5. Press down on the inhaler to release the medicine. This is called one " puff ".
6. Start breathing in SLOWLY.
7. Hold your breath for 10 seconds to allow the medicine to reach deeply into the lungs.
8. Repeat puffs as prescribed. If you can, try to wait a minute in between puffs.

How to avoid common inhaler mistakes

• Breathe in and out BEFORE pressing your inhaler
• Inhale SLOWLY
• Breathe in through your mouth, not your nose
• If you are NOT using a spacer, start inhaling BEFORE pressing down on the inhaler, and keep inhaling as you press down
• Make sure you breathe in evenly and deeply

How to clean your inhaler
It is very important to clean your inhaler and spacer regularly. Without cleaning, a build-up can occur which will stop the medicine from being delivered.

• Once a week, wash the L-shaped mouthpiece and spacer in warm, soapy water. (If you have Intal or Tilade, do not get the canister wet!)
• Rinse thoroughly.
• Let dry COMPLETELY.

What else do I need to know?
It is important to monitor expiration dates and the amount of medication remaining.

How can I tell how much medicine is left?

1. Shake the canister and listen for the sound of the remaining medication.
2. If you can, keep track of how many puffs you take. Most canisters have about 200 puffs.
3. If you want to check how much medicine is left in the canister, place it in a glass or bowl of water. Watch how it floats in the water. (This method will NOT work for Intal or Tilade. These canisters cannot get wet.)

InspirEase and E-Z Spacer
These spacers are especially helpful in delivering medications to children. After attaching the medication canister and pressing down, medicine is released into a bag which collapses when the child breathes in. Here are the steps to using the InspirEase. Be sure to read the directions that come with your spacer.

1. Connect the mouthpiece to the reservoir bag.
2. Untwist the reservoir bag to open it fully. Shake the canister and place it in the opening by the mouthpiece.
3. Place fingers on the canister or on the fingerholds of the actuation aid and pull down to release one dose (one puff).
4. Breathe in slowly (if you hear a whistle sound, you are breathing too fast!). The bag will collapse as the medication is inhaled.
5. If possible, have the child hold his/her breath before exhaling
6. Repeat as directed.

Nebulizers

What is a nebulizer?
A nebulizer is a device driven by a compressed air machine that changes a liquid medicine into a mist so it can be breathed into the lungs. It consists of a cup, a mouthpiece attached to a T-shaped part or a mask, and thin, plastic tubing to connect to the compressed air machine.

Important points to remember:

There are many different types of nebulizers available, so always follow the instructions that are provided with your machine. It usually takes about 10 minutes to complete a nebulized treatment. The liquid medicine must be stored as directed. The nebulizer MUST be cared for after each use. Cleaning gets rid of germs that can cause infections, and it also keeps the nebulizer from clogging up. Thorough DRYING of all of the parts after cleaning is essential.

How to use a nebulizer

1. If your medicine is NOT premixed: Using a clean dropper, measure the right amount of saline and place into the nebulizer cup. Then, with a different dropper, measure the right amount of medicine and place into the cup. Be sure not to confuse the two droppers.
2. If your medicine is premixed, measure the correct amount and place into the nebulizer cup.
3. Connect the mouthpiece to the T-shaped part and then fasten this to the cup. If your child is less than 2 and you are using a mask, fasten this to the cup.
4. Put the mouthpiece into the child's mouth between the teeth and sealed lips. Or place the mask on the child's face.
5. Turn on the nebulizer.
6. Take slow, deep breaths through the mouth.
7. If possible, hold each breath for 1-2 seconds.
8. Continue slow breathing for 10 minutes, or until the medicine is gone.
9. Care for the nebulizer after each use paying close attention to the thorough DRYING of all parts.

Caring for your nebulizer

After each use: rinse

1. Remove the mask or mouthpiece and T-shaped part from the cup.
2. Remove the tubing and set it aside. The tubing should not be washed or rinsed.
3. Rinse the mask or mouthpiece and T-shaped part in warm running water for 30 seconds. Use distilled or sterile water for rinsing, if possible.
4. Shake off excess water. Air dry COMPLETELY on a clean cloth or paper towel.
5. Put the mask or mouthpiece and T-shaped part, cup, and tubing back together, and connect the device to the compressor. Run the machine for 10 to 20 seconds to dry the inside of the nebulizer.
6. Disconnect the tubing from the compressor. Store the nebulizer in a sealable plastic bag.
7. Place a cover over the compressor.

Once every day: wash
Wash the mask or mouthpiece and T-shaped part with a mild dishwashing soap and hot water. If your manufacturer's instructions allow, you may use an automatic dishwasher. Rinse well.

Once or twice a week after washing and rinsing: disinfect

1. Wash your hands
2. Read and follow the manufacturer's instructions on disinfection. If the manufacturer's instructions allow, disinfect the nebulizer using one of these options:
   • Boil for 5 minutes
   • Microwave (in water) for 5 minutes
   • Dishwasher (water temperature above 158º) for 30 minutes
   • Soak in a solution of 1 part household bleach and 50 parts water for 3 minutes
   • Soak in 70% isopropyl alcohol for 5 minutes
   • Soak in 3% hydrogen peroxide for 30 minutes.
   Do not use a nebulizer that cannot be disinfected using one of these options.
3. Rinse the nebulizer parts and the eyedropper or syringe under warm running water for 1 minute. Use sterile water for the last rinse. To make sterile water, boil it for 5 minutes. (If you disinfect by boiling, you do not need to rinse the nebulizer.)
4. Shake off the water and air dry COMPLETELY on a clean cloth or paper towel.
5. Put the mask or mouthpiece and T-shaped part, cup, and tubing back together, and connect the device to the compressor. Run the machine for 10 to 20 seconds to dry the inside of the nebulizer thoroughly.
6. Disconnect the tubing from the compressor. Store the nebulizer in a sealable plastic bag.
7. Clean the surface of the compressor with a well-wrung, soapy cloth or sponge. You could also use an alcohol or disinfectant wipe. NEVER PUT THE COMPRESSOR IN WATER.
8. Place a cover over the compressor.

Measuring Peak Flow

What is a Peak Flow Meter?
A peak flow meter is a simple device that measures the amount of air you are able to exhale quickly. This can help show whether your airways are constricted (narrowed). If you can expel a lot of air quickly, your bronchial tubes are open. Regular peak flow monitoring can sometimes detect loss of lung function even before you notice the symptoms.

How to Take a Peak Flow Reading

1. Set the peak flow meter at zero.
2. Stand up tall.
3. Take a very deep breath.
4. Place the mouth piece in your mouth between your teeth and close your lips around it.
5. Blow out your mouth as hard and fast as you can (1-2 seconds).
6. Be sure not to cough or put your tongue on the mouth piece.
7. Look at the number indicated and write it down.
8. Repeat steps 1-7 two more times (3 times total).
9. Write down the highest number on your Peak Flow Diary.

How to Care for Your Peak Flow Meter

If it is dirty, rinse it with warm water. Shake out all of the water and let it dry on a towel. Make sure it is dry before you use it again. Keep it in a safe place, and don't let other kids play with it.

If Your Child Is Sick

All children occasionally get sick. It is usually OK to first try common remedies such as

• Drink additional fluids
• Get adequate rest
• Treat low grade fevers (Usually up to 101 degrees Fahrenheit, but check with your physician)
• Maintain weight by eating small frequent meals and snacks
• Understand and use the medicines prescribed regularly
• Increase chest percussion

But sometimes you need more help. Please call your physician for any of the following:

• Chest pain or acute shortness of breath
• Fever above 100 degrees Fahrenheit for more than a few days
• Blood in sputum or stool
• Diarrhea, constipation, or abdominal cramping
• Vomiting
• Notable change in activity for more than a few days
• Signs of a respiratory infection in a young child (increased cough, elevated temperature, or other signs of a cold)
• Weight loss of five pounds or greater, or a rapid weight gain
• Swollen ankles, hands, or feet

Handwashing: Your Mother Was Right

" Hand washing is the single most effective way to prevent the spread of communicable diseases ", Center for Disease Control

Why is hand washing important?
The most important thing that you can do to keep from getting sick is to wash your hands. By frequently washing your hands you wash away germs that you have picked up from other people or from contaminated surfaces.

What is good hand washing technique?
There is more to hand washing than you think! By rubbing your hands vigorously with soapy water, you pull the dirt and the oily soils free from your skin. The soapy lather suspends both the dirt and the germs trapped inside. And then the rinse water quickly washes it all away.

1. Wet your hands with warm running water.
2. Add soap, then rub your hands together, making a soapy lather. Rub your hands together, being careful to rub all of the surfaces, for about 15 seconds.
   HINT: Singing a quick chorus of "Row, Row, Row Your Boat"
   will keep you rubbing for the full 15 seconds!
3. Do this away from the running water, being careful not to wash the lather away
4. Wash the front and back of your hands,as well as between your fingers and under your nails.
5. Rinse the soap off under running water.
6. Use a paper towel to turn off the faucet in a public place.
7. Dry your hands thoroughly.
   HINT: Carry alcohol-based hand washing gels
   for places where you don't have access to soap and water.

Cystic Fibrosis Related Diabetes

What Is It?
Diabetes is a disease that may occur in a person with Cystic Fibrosis because of

• damage to the pancreas from CF
• decreased sensitivity to insulin
• or genetic factors

Fibrosis of the " endocrine " part of the pancreas can gradually lead to impaired function of specialized pancreatic cells, the insulin-producing islet cells. Insulin is a hormone critical to the body's ability to regulate blood sugar levels. (CF affects the " exocrine " portion of the pancreas, but prolonged damage may affect rest of the pancreas.)

What Happens?
People may become glucose intolerant, that is, less able to clear glucose from the bloodstream. The body is then unable to use or store food effectively; so the blood sugar level rises and can cause damage to many parts of the body.

How Would I Know if I Had It?
There may be no noticeable symptoms. Random blood or urine glucose levels may be normal.The oral glucose tolerance test (OGTT) is the most reliable method of identification. This test involves drinking a glucose (sugar) solution and measuring blood glucose at baseline and two hours later. This test should be considered for CF patients over the age of 16 on an annual basis.

What Can Be Done if I Develop Diabetes?
Management usually includes dietary modification in order to regulate the types of food eaten and the timing of food intake. In addition, insulin or oral medications may be given to lower blood sugar. Blood glucose values can be monitored at home to determine if the glucose levels are acceptable.

Vascular Access Devices

Vascular access devices are tools designed for the administration of medications, I.V. fluids, parenteral nutrition solutions, and blood products. They can also be used to take a blood sample. Some are totally implanted, such as ports, and can remain in the body for 3-5 years. Others, such as PICC lines and tunneled catheters, can be seen and accessed from the surface of the body.

Why have a vascular access device?
After repeated courses of intravenous medications, veins may become scarred, and it may become more and more difficult to find veins suitable for blood tests and administration of medication. Several different devices and procedures have been developed to provide improved access to veins.

Who should consider vascular access?

• Those who require repeated courses of intravenous antibiotics
• Those who have problems finding suitable veins
• Those whose IVs are not lasting very long

Some common types of vascular access devices

Implanted port

Implantable ports: This small device (about the diameter of a quarter and about a half inch thick) is completely under the skin, and out of the way. You will still feel a small bubble, however. It is connected to a catheter (a small flexible tube) that is placed in a large vein within the chest. You can also feel the catheter tunneled under the skin until it enters the vein.

These catheters need to be flushed at least once a month. They usually last about 3-5 years.
Disadvantages:

• There is some pain when the access needle pierces the skin to get into the bubble. This can be minimized with Emla cream.
• These devices must be placed by and removed by physicians.

Other names of ports: Mediport, BardPort, Med-Port, Infusa Port, Port-a-Cath, P.A.S. Port (this usually goes into a vein in the arm).

Tunneled Central Venous Catheters (TCVC):
The advantage of these catheters is their larger diameter, which is helpful for situations where good blood flow is required.

Tunneled catheter

The TCVC is inserted into the vascular system, then a portion of the tubing is tunneled through the subcutaneous space and exited through the skin at a convenient location on the chest. A dacron cuff just above the exit site acts as a barrier against infection and prevents the catheter from slipping out.

Disadvantages: The catheter extends several inches outside the body and needs periodic flushing. The exit site must be dept very clean to avoid infection and the dressing must be changed at least twice a week, more often if wet.

Other names of Tunneled Central Venous Catheters: Hickman, Broviac.

PICC Lines:
Peripherally Inserted Central Venous Catheters (PICC) consist of a thin plastic line that is placed into one of the large antecubital veins (inner elbow area, where blood is commonly drawn) and is threaded into the superior vena cava above the right atrium of the heart. What's nice about this catheter is that it doesn't require a surgeon to insert - an IV nurse can do it. It can also be removed by a nurse. The catheter can stay in for as long as a year. Disadvantages: The catheter needs to be flushed about once a week, if not used. With repeated use, veins can become scarred and unusable. An x-ray is needed to check the placement of a centrally placed line.

Landmark catheter:
A short catheter (3-6 inches long) that is placed into the vein with a needle. It is usually placed in the lower arm or inside the elbow. Landmark catheters usually last up to several weeks. Usually does not require an x-ray afterwards for placement.

Maintaining an Implanted Vascular Access Port

Vascular access ports are totally implantable devices that permit the infusion of medications, parenteral nutrition solutions, blood products and other fluids; ports are also useful for blood sampling. Implanted ports were developed to help provide reliable vascular access for patients who require long-term drug or fluid therapy. Ports are available in a variety of materials and designs; some maintenance is required to use these devices.

Flushing a port during intermittent infusions:
During intermittent infusions, use 5cc's of Heparin ( 10 U/cc) to flush a port.

Flushing a port that is not being accessed:
When not accessed, ports are flushed once a month with 5 cc's of Heparin ( 100 U/cc). The exception to this is a Groshong Implanted Port which is flushed monthly with 10cc's of Heparin ( 100 U/cc).

Site preparation prior to flushing:
Application of EMLA cream to numb the site 1 hour before access is highly recommended.

PORT ACCESS IS A STERILE PROCEDURE. Ports may be accessed only with a non-coring (Huber) needle. Care must be taken to follow accessing instructions carefully.

Equipment needed:

• Non-coring (Huber) needle of the proper size. Use 22g x 1 inch if unsure.
• Normal saline
• Heparin flush solution 10u/cc
• 12cc syringes with needles
• Alcohol preps
• Sterile gloves
• Sterile field
• 3 Persist swabs
• Biopatch
• TegadermHP Transparent Dressing
• 3 packages 2x2's
• Tape
• Extra needles, 25 gauge 5/8"
• Injection cap
• Safety pin

Instructions:

1. Wash your hands
2. Palpate the port until you have identified the silicone plug in the center and the metal ring which surrounds it. Be sure you can stabilize the port between your first and second fingers in order to access it.
3. Place your supplies on a clean surface which has been wiped with alcohol and allowed to dry.
4. Remove top from sterile saline vial.
5. Arrange your supplies on the sterile field.
6. Wash your hands again and don sterile gloves.
7. Draw up saline using sterile technique.
8. Flush the non-coring needle and tubing with the saline.
9. Clean skin spiraling outward to 3 inches using three Persist swabs. Do not bring the swab back to the center after you are done.
10. Palpate the port until you have identified the landmarks as above.
11. If the patient has sensitive skin, remove Persist with alcohol or normal saline.
12. Stabilize the port firmly between the first and second fingers of your non-dominant hand. Put the thumb of your dominant hand directly over the needle and push it firmly into the port until you feel the needle hit the back of the port. Aspirate for blood return.
13. Flush with 5-10 cc normal saline using a pulsing motion and leaving positive pressure in the port. Heparin lock with heparinized saline 10U/cc if port will be deaccessed and not used.
14. Place the Biopatch around the needle, grid side up.
15. If you are using a winged needle, place about 2-3 folded 2x2's under the needle wings to stabilize it. If you have a gripper needle, you won't need to place 2x2's under the needle.
16. Cover the site with the transparent dressing leaving half the T-Port outside the dressing. Loop the exposed tubing and tape on top of the dressing. If you have an IV infusion running, place some tape around the IV tubing close to the port, and pin the tubing to the shirt. (Take care not to puncture the IV tubing).
17. Document the size of the access needle and patient tolerance of the procedure. Date and initial the dressing.

Conditions to Watch For:

The site should remain clean and dry. If a port dressing becomes wet or soiled, change the dressing immediately. Watch the site carefully for any signs or symptoms of infection/phlebitis.

Possible complications:

VENOUS THROMBOSIS: a clot can form around the catheter

• Pain in the arm, neck, and/or shoulder which is noted on the same side of the body as where the port is inserted.
• Swelling may be noted above the clavicle, neck, and/or face.

CATHETER CLOTS: the catheter becomes blocked.

If the pump reads occlusion or high pressure and you have checked to make sure that there are no kinks in the line or the clamp is not on, try to flush the line with normal saline. If it flushes sluggishly, gently heparin lock the line and call the MD.

AIR EMBOLISM:

• Patient may feel chest pain or pain with deep inspiration.
• Shortness of breath or breathing rate increases.
• Skin may appear pale of blue colored around the lips and nailbeds.
• Coughing noted.

CATHETER EMBOLUS: A piece of the catheter may tear off and enter the blood stream.

• Patient may feel dizzy or faint.
• Patient may have chest pain, especially with deep inspiration.
• Patient may have shortness of breath and breathing rate increases.
• Skin may appear pale, or blue color may be noted around the lips and nailbeds.

What Is a Bronchoscopy?
By Carol Conrad, MD, Stanford CF Center

Your doctor may advise you that your child should undergo a procedure called a bronchoscopy. A bronchoscopy is a procedure that allows us to look at the airways, or the tracheobronchial tree, through a special sort of “scope”, called a bronchoscope. With the bronchoscope, we can evaluate the respiratory system, including the voice box (larynx), the wind pipe (trachea), and the airways (bronchi) for evidence of any abnormality or infection.

Why is a bronchoscopy done?

Sometimes it is important to watch the movement of these structures during the different stages of the breathing cycle. At times it is important for diagnostic purposes to obtain some of the fluids in the lung through the bronchoscope for evaluation in the laboratory. The scope has a special channel through which we can vacuum some of the liquid lining from the airways. A bronchoscopy allows a physician to perform diagnostic tests, to obtain specimens for biopsy and culture, or to remove foreign objects that children might have inhaled.

What is a bronchoscope?

The bronchoscope is a soft (flexible) tube with an outer diameter as small as 2.2 mm and there are larger sizes for use with larger children and adults. The scope can be easily passed through the nose or the mouth. The flexible tube actually contains a fiber-optic system which attaches to a video camera and a source of light. The light travels through the scope and lights up the inside of the airway. The image seen at the tip of the scope is transmitted back again through the fiber-optic system to the video camera. We can also take photographs through the scope.

What information do you get from a bronchoscopy?

A bronchoscopy enables the physician to see and test the material that is deep in a patient's lungs. Sometimes bacteria lodge deep in the lungs, and it can be difficult to find or identify them. This material can be washed out by washing the airways with saline. This is referred to as a bronchoalveolar lavage (BAL). The physician injects a small amount of saline through the bronchoscope into the airways and then sucks it back through the suction port of the bronchoscope. The fluid obtained contains saline plus secretions from the lung: bacteria (if present), cells, etc. This sample is sent to the laboratory for testing.

How is a bronchoscopy done?

A bronchoscopy is done in a special room in the outpatient ambulatory procedure unit at the Packard Children's Hospital. Typically, a bronchoscopy is performed with the patient sleeping, but breathing on their own. The patient is given medications to produce sedation (a sleepy state). At times, biopsies, or very small pieces are obtained from the lungs, and this may require the use of general anesthesia, but most bronchoscopies are done under sedation. The patient is arousable from this sleep and is able to cough, sneeze, or may try to speak if directed. We keep a close watch on the patients with monitors that continuously check the patient's vital signs such as heart rate, blood pressure, and blood oxygen levels (oximetry).

After the patient is asleep, the next step is to numb the nose and back of the throat. Numbing drops (Lidocaine) are sprayed into the nose. Later on during the procedure, this medicine can be applied to the airways though the bronchoscope to numb other structures such as the larynx, trachea, and bronchi as they are encountered. The Lidocaine prevents irritation from the scope to the airways, and can minimize coughing and sneezes. After the numbing medicine is applied, the bronchoscope is inserted through one nostril, and the procedure begins.

How long will this take?

The patient usually comes to the outpatient surgical center an hour or so before the scheduled bronchoscopy begins. This allows time to fill out insurance and medical forms, and in the pre-operative unit, vital signs are recorded, and a brief physical exam is done. At about this time, an IV line is placed by the nurses. The actual bronchoscopy takes about 45 minutes. After the procedure is done, the patient recovers in the post-anesthesia care unit until he/she is awake and is able to go home. The medicines used for sedation are considered to be “short-acting”, but parents often report that the baby sleeps through much of the rest of the day. The entire procedure takes about 4 hours in the hospital.

What are the risks of the procedure?

Flexible fiberoptic bronchoscopy is generally very well-tolerated and safe, even in very young infants. However, there are certain complications that are associated with flexible bronchoscopy. The most common problem is a fever that occurs after the procedure. This is usually a low grade fever (rarely over 101°) and usually responds to acetaminophen (Tylenol, Tempra, or other brands). Your child may experience some mild bleeding from the nose. This responds to pressure and is rarely encountered in children who are not predisposed to bleeding problems. In patients who are having a biopsy performed, a pneumothorax is a concern. This results in the collection of air around the lung and may result in collapse of a lung. A tube may need to be placed to evacuate the air and allow the lung to re-expand. Your child may require supplemental oxygen during and after the procedure. If he/she is having respiratory difficulties, we may need to place a temporary breathing tube in your child's airway and breathe for him or her. Finally, oversedation may necessitate a longer recovery period for your child and in rare instances, an overnight hospitalization.

Glossary of Terms

A

Airway Clearance
The removal of mucus secretions from the lungs by coughing or other methods.

Anti-inflammatory
Something that stops swelling

Antibiotics
Medicines that kill bacteria (not viruses)

B

Bronchodilator
Medicine that opens and relaxes the lungs to aid breathing.

C

Carrier
Someone that has one CF gene instead of two. They do not have CF but can give it to their child. For a child with CF, each parent either has CF (two CF genes) or is a carrier (one CF gene).

Chest clearance therapies
Treatments to clear lung mucus (chest physiotherapy, the Vest™, the Flutter®, Acapella™, etc.).

Chest physiotherapy (CPT)
Treatment to break up and loosen lung mucus so that it can be coughed out.

Chronic
Lasting a long time. CF is a chronic disease. The opposite of "chronic" is "acute".

D

Ducts
Tubes or pathways for secretions. Ducts are found in organs, organ systems, and glands. In CF, thick mucus can clog ducts and block secretions.

E

Enzymes
Enymes help to break down foods during digestion. In CF, mucus can block the tube that carries enzymes from the pancreas to the food. People with CF may take extra enzymes to help digest their food.

G

Gastrointestinal
Relating to the stomach and intestines

Gene
The basic unit of heredity. Genes decide a big part of what people are like (eye color, looks, height, health). CF is caused by a defect of a gene. If the Dad's sperm has a CF gene and the Mom's egg has a CF gene, the child will have CF.

Genetic
Having to do with genes (See "Gene"). A trait passed on from one family member to another.

Germs
Viruses or bacteria

Glands
A cell, group of cells, or organ that makes a secretion for use in the body

H

Hormone
A secretion of certain glands. Hormones manage body functions like growth, maturing, and heart rate. Hormones are not affected by CF.

I

Immunizations
Shots needed to protect from illness

Infection control
Stopping the spread of illness by washing, cleaning, avoiding sick people, etc.

Inflammation
The swelling of body tissues due to irritation or injury. Inflammation is a process by which the body's white blood cells and chemicals protect us from infection and foreign substances such as bacteria and viruses. Inflammation occurs with an infection.

Intestinal blockage
Something that blocks the flow of food or feces in the intestines

M

Malabsorption
Poor uptake of nutrients from food for use by the body. In CF, mucus can plugs the ducts that carry the enzymes and hormones used in digestion. The body can't digest food as well so doesn't get the nutrients from the food. The body needs nutrients for health and growth. A common symptom of CF is failure to thrive.

Median
The middle point in a line of values. Above and below the median are an equal number of values. In "1   4   5   9   12", "5" is the median. Two numbers are above the 5, and two numbers are below it.

Mucus
A thin, slippery fluid made by mucus membranes and glands. In CF, mucus is often thick and sticky.

N

Nutrition supplements
Pills, fluids, snacks, and drinks that give the body extra nutrition.

P

Pancreas
Long gland-like organ found behind the stomach. The duct part of the pancreas secretes enzymes into the intestine to help break down food. In CF, mucus may clog the ducts and block digestion. The other part of the pancreas contains endocrine tissue, which makes the hormone insulin. Insulin controls how the body uses and stores sugar.

Pancreatic duct
See "Pancreas"

Pancreatic Enzyme Supplements
See "Enzymes"

S

Secretions
See "Mucus"