Mucoviscidosis

Congenital multiorgan disease affecting mainly the lungs, liver, and pancreas. Frequent lung infections, hemoptysis, intolerance to exercise, presence of clubbing fingers suggesting pulmonary hypertension, rectal prolapse, and nasal polyps.

Cystic Fibrosis (CF).

In the United States, CF is the most common lethal disease inherited in the white population. In America and Northern European origin, the prevalence is estimated at 1:3000. In African Americans, the prevalence is 1:15,000 whereas in hispanics, it is estimated at 1 case per 9200. In Asian Americans, the prevalence is reported at 1 case per 31,000.

Autosomal recessive. More than 1000 mutations have been described on the long arm of chromosome 7 (7q21.3-7q22.1); the most frequent is ΔF508, which results in a defect of the CF transmembrane regulator protein called CFTR.

Malfunction of the gene coding for the CF transmembrane conductance regulator (CFTR) protein causes defective cAMP-dependent chloride secretion from the epithelium of different exocrine tissues, leading to thick viscous and difficult-to-clear secretions in lungs, sinuses, pancreas, intestine, liver, and reproductive tract. In addition, the CFTR-mediated regulation of sodium channel activity may fail, leading to increased sodium absorption from the airways, which contributes to the fluidity and mobilization of the airway secretions. Also, hyperplastic airway epithelium with areas of erosion and squamous metaplasia of the submucosal glands leads to plug of mucoid material and subsequently to the release of inflammatory cells. Eventually, grossly dilated airways with purulent secretions are observed and severely congested parenchyma develops. Radiologic findings reflect the pathologic changes in the airways. Although the lungs of infants born with CF are structurally normal at birth, respiratory symptoms are usually the first sign of CF.

Difficult in children. Depends on the clinical history and a high index of suspicion together with a family history of the disease; a high sweat sodium concentration greater than 60 mmol/l, or abnormal in vivo nasal potential difference. A normal nasal potential difference value is 0. 9-24.7 mV, whereas an abnormal measurement is 1.8-53 mV (difference of potential voltage difference between the nasal mucosa and a reference electrode into the forearm). Absent vas deferens and epididymis in the male. Immunoreactive trypsin.

CF is now the most common cause of recurrent bronchopulmonary infection in childhood and is an important cause in early adult life. Finger clubbing is almost universal, hemoptysis is frequent, and breathlessness occurs in the later stages as airflow limitation develops. Older children may develop nasal polyps. Gastroesophageal reflux is often present. Puberty and skeletal maturity are delayed in most patients with the disease. Males are always infertile as a result of failure of development of the vas deferens and epididymis. Females are able to reproduce, but often develop secondary amenorrhea as the disease progresses. Approximately 85% of patients have symptomatic steatorrhea because of pancreatic dysfunction. Children may be born with meconium ileus because of the viscoid consistency of meconium in CF and later in life develop the meconium equivalent (MIE) syndrome, an important cause of small bowel obstruction unique to CF. Cholesterol gallstones appear to occur with increased frequency, and biliary cirrhosis with portal hypertension develops in approximately 5 to 10% of older patients. Diabetes mellitus occurs in 20% of adults. Risk of spontaneous pneumothorax increases with age; pleurodesis is sometimes necessary. Ventilation/perfusion inequality is prominent as the disease progresses.

Many of these children become severely emotionally upset. They require careful attention and much reassurance. Assess the patient's condition carefully: clinical examination (dyspnea, productive cough, hepatosplenomegaly), pulse oximetry while breathing room air (and arterial blood gases if hypoxemia; check PaCO2), chest radiograph (emphysema, bubbles, infection), blood glucose and electrolytes, and renal and liver function tests. Chronic respiratory disease may result in cor pulmonale. Do not give opiates as premedication. Give benzodiazepines cautiously if indicated to counter anxiety. Ensure optimal hydration; fluids must not be withheld for long periods of time. Order chest physiotherapy immediately before anesthesia and postoperatively. Strongly suspect chronic colonization of lungs with antibiotic-resistant Pseudomonas or Staphylococcus species, or even Aspergillus.

Copious, extremely viscous secretions in the respiratory tract; nebulization of recombinant human DNAse is very helpful in decreasing their viscosity. Hypoxia may develop rapidly because of V/Q disturbances, and induction of anesthesia is prolonged. Lung compliance is reduced. In severe advanced cases, very high airway pressure may be required to provide adequate ventilation and prevent hypoxemia. Therefore, use a cuffed endotracheal tube whenever possible. Use local or regional anesthesia wherever possible. If general anesthesia is given, administer 100% O2 for at least 5 minutes, then intravenous induction. Tracheal intubation; use cuffed tube; suction as often as necessary to prevent blocking by thick plugs, and use as high an FiO2 (fraction of inspired oxygen) as necessary (may need 100%). Prevent hyperventilation and be aware of the risk of gas trapping. High risk for bronchial hyperreactivity and pneumothorax. Avoid long-acting opioids for postoperative pain relief, but effective analgesia is mandatory to allow chest physiotherapy. Use regional anesthesia for postoperative pain relief if possible. Aim for early postoperative emergence from anesthesia. Note the importance of postoperative fluids and a humid environment, as well as of physiotherapy. Encourage the patient to cough. Long postoperative ileus or even subocclusive episodes possible even in the absence of surgical complication.

Use of anticholinergic agents is controversial (risk of inspissated secretions), and ketamine is best avoided (increased bronchial secretions). Malnutrition and underweight for age are common as a result of chronic infection or malabsorption therefore, drug dosages must be adjusted accordingly. Mild liver dysfunction is not unusual. Drug dosages should be adapted accordingly.

Lubani Al Saleh Teebi Syndrome: Cystic fibrosis with Helicobacter pylori gastritis, megaloblastic anemia, and subnormal mentality.

α1-Antitrypsin Deficiency (AATD): Relatively common inherited disorder; primarily presents with early-onset panacinar lung emphysema and in a minority of the patients also with liver cirrhosis. Cardiac arrest in association with general anesthesia has been described.

Kartagener Syndrome: Genetically transmitted polymalformative syndrome characterized by bronchiectasis, situs inversus, and chronic sinusitis.