Cystic fibrosis, a complex, systemic autosomal recessive disease affects the respiratory, digestive and exocrine systems in the body. The treatment requires long term antibiotics, anti-inflammatories, mucolytics, etc. along with psychological counselling and lifestyle changes. This article explains the disease and highlights the recommendations for treatment.

---

Cystic fibrosis affects the functions of the respiratory system, digestive tract and all exocrine glands. The disease occurs is due to a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. About 10% of the patients are diagnosed at birth and about 60-70% of the patients are diagnosed before one year of age.

---

Clinical symptoms

Respiratory symptoms predominate the clinical picture in patients with cystic fibrosis and determine the prognosis in more than 90% of patients.

Symptoms and manifestations most commonly include the upper respiratory tract - chronic rhinitis/rhinorrhea, nasal polyposis, sinusitis and involvement of the lower respiratory tract, with the early symptom being chronic cough, whooping cough, wet rales, obstructive pulmonary disease (wheezing, tachydispnea) with bronchial hyperreactivity in 50% of cases.

Late respiratory symptoms include:

• Respiratory failure
• Exacerbation of respiratory distress
• Hypercapnia
• Pulmonary hypertension
• Cor pulmonale

Children present with typical characteristic symptoms, such as:

• Retardation in physical development
• Dystrophic changes of skin and hair
• Enlarged, often deformed chest
• Large abdomen (sometimes the occurrence of umbilical hernia)
• Thin limbs with deformed extremities of the fingers

With severe disease, the processes in the lungs constantly progress, exacerbations occur more often, phlegm is purulent, with a rotten odour. The bronchial obstructive syndrome is severe and is associated with a narrowed lumen of the bronchi as a result of inflammatory changes in the bronchial wall and the accumulation of viscous secretions.

In the evolution of the disease, the symptoms of hypoxia gradually increase - shortness of breath, cyanosis, tachycardia, the cor pulmonale, respiratory and heart failure develop.

---

Pulmonary function tests

Pulmonary function is an important measure of disease severity and prognosis in cystic fibrosis patients. Spirometry should be performed for measurement of FVC (forced life capacity), FEV1 (forced expiratory volume for 1 sec), FEF25-27 (forced expiratory flow between 25% and 75% of vital capacity). FEV1 is the most proven clinical means of lethal prognosis and is the primary means of measuring the outcome.

---

Treatment guidelines

Complex therapy includes bronchodilators, NSAIDs and corticosteroids. Respiratory rehabilitation is often required in combination with general body massage.

The purpose of therapy is to control lung infections and improve nutritional status and delay definitive changes. Evacuation of the bronchial secretion is achieved by oral mucolytic agents – N-acetylcysteine, Ambroxol and others. Inhalation therapy with mucolytics is also used. Pulmozyme (dornase-α) is also included in the treatment of all patients with cystic fibrosis after the age of 5, modifying the abnormal viscosity and elasticity of the phlegm, improving the clearance of lung secretions. In the absence of effect and increase in bronchial obstruction, a therapeutic bronchoscopy is performed.

Antibiotic oral courses (but lasting 2–4 weeks) are sometimes sufficient. For more severe infections, intravenous administration is required. Chronic P. aeruginosa infection is associated with faster progression and impaired pulmonary function. Therefore, at first colonisation with P. aeruginosa, the behaviour should be extremely aggressive for eradication - for example, 3 months oral administration of ciprofloxacin in combination with colistin inhalation.

In patients suffering from chronic P. aeruginosa infection, the growth pattern in the form of a biofilm means that the bacterium is never completely destroyed. Therefore, the therapeutic goal is chronic bacterial suppression, a strategy not commonly used in other patient groups. However, intensive and early antibiotic therapy is used in many countries, which is effective in eradicating the first or intermediate colonies of P. aeruginosa in all age groups.

Certain bacterial species can cause cross-contamination among patients at CF centres or during social activities. Sputum microbiological examination in patients with cystic fibrosis should be performed at least once every 3 months.

---

Kinesitherapy

One of the important components of CF treatment is kinesitherapy. Depending on their health status, patients with cystic fibrosis may perform locomotor activity in hospitals under the guidance of paramedics (respiratory rehabilitation), at home (adapted physical activity), at school or in sports. Its main purpose is to clear the bronchial tree from the viscous secretion.

The tasks of kinesitherapy are to relax the respiratory muscles and the diaphragm, reduce the frequency of breathing and control the exhalation, facilitate the removal of the bronchial secretion and its evacuation by increasing the volume of bronchial oscillations and the speed of airflow, improving exercise mobility in coughing and expectoration and training in compensatory diaphragmatic breathing.

---

Guidelines for advanced CF lung disease

Following are the highlights of the checkpoints to be taken care of while treating a patient with cystic fibrosis:

1. Routine advance care planning conversations with patients and their caregiver(s), should be done including communication about prognosis and goals of care, documentation of advance directives, and decision-making surrounding lung transplantation.
2. Screening for hypoxemia should be done on exertion and sleep, hypercarbia, and pulmonary hypertension.
3. Supplemental oxygen must be given for individuals with ACFLD and exercise-induced or nocturnal hypoxemia.
4. Nocturnal non-invasive ventilation for individuals with ACFLD and chronic hypercarbia should be considered.
5. Lung transplantation can be considered as a treatment option for individuals with ACFLD if congruent with the goals of care.
6. Individuals with ACFLD and acute respiratory failure should be considered eligible for intensive care unit management regardless of transplant status if congruent with goals of care.
7. Individuals with ACFLD and acute respiratory failure should be considered for a trial of high flow nasal cannula oxygen and/or noninvasive ventilation.
8. For individuals with ACFLD and acute respiratory failure requiring invasive mechanical ventilation, the CF Foundation recommends consideration of early tracheostomy when the anticipated need for mechanical ventilation is more than 5-7 days.
9. Individuals who develop refractory respiratory failure requiring invasive mechanical ventilation should be considered for early transition to extracorporeal membrane oxygenation (ECMO) support.
10. Inhalational antibiotics should be administered as dictated by bacterial pathogens identified in the respiratory culture.
11. Screening for fungal pathogens should be done in addition to standard microbiological screening.
12. Patients should be encouraged for pulmonary rehabilitation programs.
13. Using systemic corticosteroids should be considered.
14. Routine screening for gastroesophageal reflux (GER) should be kept in mind.
15. The use of enteral tube feeds should be advised for individuals with ACFLD and malnutrition after consideration of procedural risks versus benefits.
16. For individuals with ACFLD with frequent prior and continuing exposure to nephrotoxic and ototoxic agents, the CF Foundation recommends increased monitoring for accumulating toxicity.
17. Women with ACFLD contemplating pregnancy should consider the risks in consultation.
18. For individuals with ACFLD with indications for opioids, the CF Foundation recommends a treatment that includes monitoring for adverse effects, and consultation with pain and/or palliative care specialists as appropriate.
19. For individuals with ACFLD and anxiety, the CF Foundation recommends screening and treating depression and anxiety with benzodiazepines.

---

Medications

Bronchodilators:

• β 2 agonists
• Anticholinergics

Inhaled antibiotics:

• Tobramycin: Mild, moderate to severe lung disease
• Aztreonam: Mild, moderate to severe lung disease

Systemic antibiotics:

• Anti-Staphylococcus aureus agents for chronic and prophylactic uses
• Anti-Pseudomonas aeroginosa agents for chronic use

Mucolytics:

• Dornase alpha
• Hypertonic saline

Anti-inflammatory

• Inhaled corticostreroids
• Oral corticosteroids
• Ibuprofen
• Azithromycin
• Leukotriene modifiers
• N-acetyl cysteine
• Inhaled glutathione

CFTR modulators:

• Ivacaftor: Especially in patients with at least one copy of the G551 CFTR mutation

---

Complications

1. As the disease progresses, complications and conditions may be observed that require immediate intervention. These include atelectasis, pneumothorax and pulmonary haemorrhage.
2. In asymptomatic patients, if pneumothorax is detected by chance, the patient is actively observed for 24 hours and if clinical symptoms do not appear and the changes do not progress radiologically, regular follow-up may be initiated.
3. In all other cases, drainage, surgery, pleurodesis, locally sclerosing agents, pleural abrasion may be required.

---

Cystic fibrosis is a complex disease that requires a holistic treatment approach. In recent years, medicine has progressed significantly with CF with regard to a dramatic improvement in life expectancy.

Nowadays, the expectation of children suffering from cystic fibrosis to survive more than 60 years comes with the cost of heavy, intensive daily treatment, which should not be interrupted. Adequate day-to-day treatment is expensive and very time-consuming, with frequent hospital visits also making a negative impression.

The establishment of specialised centres with trained and experienced professionals is essential in order to provide optimal patient care. These include frequent clinical evaluations, follow-up of complications, and early interventions for the treatment of patients with cystic fibrosis.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.