Cystic Fibrosis

Epidemiology

• Synonyms: mucoviscidosis, fibrosa cystica
• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency differs significantly among ethnicities:
  • Caucasians: 1 in 3,000–4,000 live births
  • Latin Americans: 1 in 4,000–10,000 live births
  • African Americans: 1 in 15,000–20,000 live births
  • Asian Americans: 1 in 30,000 live births
• Most common autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance disease in White populations
• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in the United States: 1 in 3,400 live births
• Cystic Cystic Fibrocystic Change fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans (CF) screening Screening Preoperative Care is part of the newborn Newborn An infant during the first 28 days after birth. Physical Examination of the Newborn screening Screening Preoperative Care in many countries with a high prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of the condition.
• More than 75% of people with CF are diagnosed by the age of 2.

Etiology and Pathophysiology

Etiology

• Autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance inheritance 
• Over 1,500 causative mutations have been identified.
• Mutations are noted on chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 7, which encodes the cystic Cystic Fibrocystic Change fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans transmembrane conductance regulator (CFTR) protein.
• More than 2,000 mutations in the CFTR gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics can cause disease.
• The most common mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in Central Europe and North America is the delta F508 mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations on chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 7. This deletion causes the loss of phenylalanine Phenylalanine An essential aromatic amino acid that is a precursor of melanin; dopamine; noradrenalin (norepinephrine), and thyroxine. Synthesis of Nonessential Amino Acids in position 508.

• The type of mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations is crucial in determining the severity of the disease.
  There are 5 distinct classes:
  • Class I: No gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics expression of CFTR; the messenger RNA Messenger RNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure ( mRNA mRNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure) is terminated, so no CFTR protein is produced.
  • Class II: The CFTR channel can be constructed, but there is a defect in posttranslational processing. The unstable protein is degraded by proteasomes and thus cannot be built into the membrane (applies to the delta F508 mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations).
  • Class III: The channel is expressed and built in but cannot open due to a gating mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations (so there is no chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure). 
  • Class IV: The protein is produced and localized in the membrane but the channel does not open properly. (defective chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes conductance by reducing ion flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure and duration of opening).
  • Class V: change in the stability of the mRNA mRNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure producing less functional CFTR protein. In some cases, the instability is in the CFTR protein (and is classified as class VI).
• Class I, II, and III mutations result in more classic and severe disease.
• CFTR encodes an important component of the ATP-gated chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes channel in cell membranes.
  • Usually found in epithelial cells throughout the body (e.g., gastrointestinal and respiratory epithelia, sweat glands Sweat glands Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. Soft Tissue Abscess, exocrine pancreas Exocrine pancreas The major component (about 80%) of the pancreas composed of acinar functional units of tubular and spherical cells. The acinar cells synthesize and secrete several digestive enzymes such as trypsinogen; lipase; amylase; and ribonuclease. Secretion from the exocrine pancreas drains into the pancreatic ductal system and empties into the duodenum. Pancreas: Anatomy, exocrine glands Exocrine glands Glands of external secretion that release its secretions to the body’s cavities, organs, or surface, through a duct. Glandular Epithelium: Histology of reproductive organs)

Pathophysiology

• Mutated CFTR → absent or dysfunctional chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes channel → dysfunctional transport of chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes → abnormal secondary transport of sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia and water
• In sweat glands Sweat glands Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. Soft Tissue Abscess: inability to reabsorb chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes from the lumen → reduced reabsorption of sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia and water → sweat with elevated levels of sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes + excessive loss of salt
• In rest of exocrine glands Exocrine glands Glands of external secretion that release its secretions to the body’s cavities, organs, or surface, through a duct. Glandular Epithelium: Histology: inability to secrete chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes into the lumen → accumulation of intracellular chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes → increased sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia and water reabsorption → formation of hyperviscous mucus → accumulation of secretions → blockage of small passages → chronic inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation → multiple organ damage

Impact on organ systems

• Lung:
  • Ineffective mucociliary clearance Mucociliary clearance A nonspecific host defense mechanism that removes mucus and other material from the lungs by ciliary and secretory activity of the tracheobronchial submucosal glands. It is measured in vivo as mucus transfer, ciliary beat frequency, and clearance of radioactive tracers. Acute Bronchitis; obstruction of the alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS)/ bronchioles Bronchioles The small airways branching off the tertiary bronchi. Terminal bronchioles lead into several orders of respiratory bronchioles which in turn lead into alveolar ducts and then into pulmonary alveoli. Bronchial Tree: Anatomy with an increased risk of infection 
  • Destruction of the lung and reformation into a honeycomb parenchymal pattern due to chronic inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation
• Pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy:
  • Blockage of the exocrine gland’s secretion Secretion Coagulation Studies outlets
  • Fibrotic and cystic Cystic Fibrocystic Change mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations
  • Loss of exocrine function
• Gallbladder Gallbladder The gallbladder is a pear-shaped sac, located directly beneath the liver, that sits on top of the superior part of the duodenum. The primary functions of the gallbladder include concentrating and storing up to 50 mL of bile. Gallbladder and Biliary Tract: Anatomy:
  • Obstruction of bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy drainage
  • Development of biliary cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
• Intestines:
  • Obstipation Obstipation Large Bowel Obstruction

Clinical Presentation

Respiratory system

• Chronic/recurrent sinus infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, nasal polyps
• Recurrent pulmonary infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, especially with Pseudomonas Pseudomonas Pseudomonas is a non-lactose-fermenting, gram-negative bacillus that produces pyocyanin, which gives it a characteristic blue-green color. Pseudomonas is found ubiquitously in the environment, as well as in moist reservoirs, such as hospital sinks and respiratory equipment. Pseudomonas aeruginosa 
  • Increasing lung insufficiency leads to exertional dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, anoxia, and bronchiectasis Bronchiectasis Bronchiectasis is a chronic disease of the airways that results from permanent bronchial distortion. This results from a continuous cycle of inflammation, bronchial damage and dilation, impaired clearance of secretions, and recurrent infections. Bronchiectasis
  • Clubbing Clubbing Cardiovascular Examination of fingers and nails
  • 10%–50 % of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship develop polyposis nasi and chronic pansinusitis 
  • Expiratory wheezing Wheezing Wheezing is an abnormal breath sound characterized by a whistling noise that can be relatively high-pitched and shrill (more common) or coarse. Wheezing is produced by the movement of air through narrowed or compressed small (intrathoracic) airways. Wheezing and barrel chest

Gastrointestinal system

Reproductive system

• Males
  • Infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility and delayed secondary sexual development Secondary Sexual Development Delayed Puberty due to:
    • Obstructive azoospermia Azoospermia A condition of having no sperm present in the ejaculate (semen). Infertility due to bilateral aplasia Aplasia Cranial Nerve Palsies/ atresia Atresia Hypoplastic Left Heart Syndrome (HLHS) of the deferent duct
    • Undescended testicle; 15 times more likely than in the general population 
• Females
  • Reduced fertility due to:
    • Viscous cervical mucus 
    • Amenorrhea Amenorrhea Absence of menstruation. Congenital Malformations of the Female Reproductive System

Urinary system

• Nephrolithiasis Nephrolithiasis Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis
• Stress incontinence Stress incontinence Involuntary discharge of urine as a result of physical activities that increase abdominal pressure on the urinary bladder without detrusor contraction or overdistended bladder. The subtypes are classified by the degree of leakage, descent and opening of the bladder neck and urethra without bladder contraction, and sphincter deficiency. Urinary Incontinence (frequent coughing)

Mnemonic device

To recall the most common clinical features of cystic Cystic Fibrocystic Change fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans, remember the acronym CF PANCREAS Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy:

• C: Chronic cough
• F: Failure to thrive Failure to Thrive Failure to thrive (FTT), or faltering growth, describes suboptimal weight gain and growth in children. The majority of cases are due to inadequate caloric intake; however, genetic, infectious, and oncological etiologies are also common. Failure to Thrive
• P: Pancreatic insufficiency (exocrine)
• A: Alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis and hypotonic Hypotonic Solutions that have a lesser osmotic pressure than a reference solution such as blood, plasma, or interstitial fluid. Renal Sodium and Water Regulation dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration
• N: Nasal polyps, neonatal dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration
• C: Clubbing Clubbing Cardiovascular Examination of fingers (Hippocratic fingers and nails)
• R: Rectal prolapse Rectal prolapse Rectal prolapse, also known as rectal procidentia, is the protrusion of rectal tissue through the anus. The tissue may include just the mucosa or the full thickness of the rectal wall. Common risk factors include chronic straining, constipation, bowel motility disorders, and weakening of the pelvic floor muscles. Rectal Prolapse
• E: Electrolyte elevation (sweat)
• A: Atresia Atresia Hypoplastic Left Heart Syndrome (HLHS), absence of vas deferens Vas Deferens The excretory duct of the testes that carries spermatozoa. It rises from the scrotum and joins the seminal vesicles to form the ejaculatory duct. Testicles: Anatomy
• S: Sputum with Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus or Pseudomonas Pseudomonas Pseudomonas is a non-lactose-fermenting, gram-negative bacillus that produces pyocyanin, which gives it a characteristic blue-green color. Pseudomonas is found ubiquitously in the environment, as well as in moist reservoirs, such as hospital sinks and respiratory equipment. Pseudomonas

Complications

Diagnosis

Newborn Newborn An infant during the first 28 days after birth. Physical Examination of the Newborn screening Screening Preoperative Care

• CF testing is part of the newborn Newborn An infant during the first 28 days after birth. Physical Examination of the Newborn screening Screening Preoperative Care in most high-prevalence countries (North America, Australia, many European countries).
• Involves multiple steps of testing on dried blood spots
• Measurement of immunoreactive trypsinogen Trypsinogen The inactive proenzyme of trypsin secreted by the pancreas, activated in the duodenum via cleavage by enteropeptidase. Pancreatic Parameters, if positive → mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations analysis of CFTR
• If results indicate CF, the next step is a sweat chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes test when the infant is at least 2 weeks of age and weighs over 2 kg.

Sweat chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes test: gold standard of diagnosis 

•   Pilocarpine Pilocarpine A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma. Cholinomimetic Drugs iontophoresis used to determine sweat chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes concentration
•  ≥ 60 mmol/L in 2 tests: diagnosis of CF

Further testing

If the diagnosis remains unclear, further testing can be done.

Nasal potential difference:

• Specialized test only at CF centers; further evaluates CFTR dysfunction
• Electrodes Electrodes Electric conductors through which electric currents enter or leave a medium, whether it be an electrolytic solution, solid, molten mass, gas, or vacuum. Electrocardiogram (ECG) are placed in the nasal cavity Nasal cavity The proximal portion of the respiratory passages on either side of the nasal septum. Nasal cavities, extending from the nares to the nasopharynx, are lined with ciliated nasal mucosa. Nose and Nasal Cavity: Anatomy, which is then bathed in a series of solutions with different salts designed to change ion flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure across the membrane in predictable ways.
• Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with CF have a more negative baseline difference and react differently to the other salts because of defective chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes transport.

Intestinal current measurements (ICM):

• Can be performed on patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship of all ages, including newborns
• Rectal suction biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma is obtained.

Fecal elastase Elastase A protease of broad specificity, obtained from dried pancreas. Molecular weight is approximately 25, 000. The enzyme breaks down elastin, the specific protein of elastic fibers, and digests other proteins such as fibrin, hemoglobin, and albumin. Proteins and Peptides:

Pancreatic insufficiency can be detected when screening Screening Preoperative Care the stool for pancreatic elastase-1 Elastase-1 A protease of broad specificity, obtained from dried pancreas. Molecular weight is approximately 25, 000. The enzyme breaks down elastin, the specific protein of elastic fibers, and digests other proteins such as fibrin, hemoglobin, and albumin. Pancreatic Parameters, which is absent in 80% of people with CF.

Imaging:

• Sinus CT: panopacification, nasal polyps
• Chest CT: bronchiectasis Bronchiectasis Bronchiectasis is a chronic disease of the airways that results from permanent bronchial distortion. This results from a continuous cycle of inflammation, bronchial damage and dilation, impaired clearance of secretions, and recurrent infections. Bronchiectasis typically in upper lobes, may progress to be visible on radiographs

Airway Airway ABCDE Assessment culture:

• Persistent detection of the following bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology in respiratory secretion Secretion Coagulation Studies and sputum
• 80% grow S. aureus S. aureus Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. Staphylococcus or Pseudomonas Pseudomonas Pseudomonas is a non-lactose-fermenting, gram-negative bacillus that produces pyocyanin, which gives it a characteristic blue-green color. Pseudomonas is found ubiquitously in the environment, as well as in moist reservoirs, such as hospital sinks and respiratory equipment. Pseudomonas aeruginosa
• Haemophilus Haemophilus Haemophilus is a genus of Gram-negative coccobacilli, all of whose strains require at least 1 of 2 factors for growth (factor V [NAD] and factor X [heme]); therefore, it is most often isolated on chocolate agar, which can supply both factors. The pathogenic species are H. influenzae and H. ducreyi. Haemophilus influenzae, Burkholderia Burkholderia Burkholderia species are gram-negative bacilli with 2 clinically relevant pathogens: B. pseudomallei (causing melioidosis) and B. cepacia complex (causing opportunistic infections). Melioidosis is commonly seen in Asia and Australia. Infection is transmitted by contact with contaminated soil or water (via skin wounds). Burkholderia cepacia, Stenotrophomonas maltophilia
  • All (except S. aureus S. aureus Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. Staphylococcus) would be unusual in healthy people without CF

Management

Management of CF should be multidisciplinary and include specialized physicians Physicians Individuals licensed to practice medicine. Clinician–Patient Relationship, physiotherapists, dieticians, and/or psychological support.

Prognosis

• With optimal treatment, CF patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have a median life expectancy Life expectancy Based on known statistical data, the number of years which any person of a given age may reasonably expected to live. Population Pyramids of 45 years.
• 50% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship die before the age of 18 from respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure.
• The prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas depends on several factors:
  • Age 
  • Female sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria
  • Gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics variant 
  • Colonization Colonization Bacteriology by multidrug-resistant pathogens 
  • Lung function
  • Complications
  • Access to medical care Medical care Conflict of Interest 

Differential Diagnosis

The following conditions are related to cystic Cystic Fibrocystic Change fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans:

• Bronchiectasis Bronchiectasis Bronchiectasis is a chronic disease of the airways that results from permanent bronchial distortion. This results from a continuous cycle of inflammation, bronchial damage and dilation, impaired clearance of secretions, and recurrent infections. Bronchiectasis: a chronic condition in which the bronchi Bronchi The larger air passages of the lungs arising from the terminal bifurcation of the trachea. They include the largest two primary bronchi which branch out into secondary bronchi, and tertiary bronchi which extend into bronchioles and pulmonary alveoli. Bronchial Tree: Anatomy walls thicken as a result of inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and infection. This condition is characterized by the permanent enlargement of sections of the airways within the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship often have flare-ups of breathing difficulties, displaying chronic cough with mucus production.
• Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia: acute or chronic inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of lung tissue caused by infection with bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology, viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology, or fungi Fungi A kingdom of eukaryotic, heterotrophic organisms that live parasitically as saprobes, including mushrooms; yeasts; smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi, commonly known as molds, refer to those that grow as multicellular colonies. Mycology. Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia can be also due to toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy.
• Malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion: a disorder involving the inability to absorb nutrients from food, such as carbohydrates Carbohydrates A class of organic compounds composed of carbon, hydrogen, and oxygen in a ratio of cn(H2O)n. The largest class of organic compounds, including starch; glycogen; cellulose; polysaccharides; and simple monosaccharides. Basics of Carbohydrates, fats Fats The glyceryl esters of a fatty acid, or of a mixture of fatty acids. They are generally odorless, colorless, and tasteless if pure, but they may be flavored according to origin. Fats are insoluble in water, soluble in most organic solvents. They occur in animal and vegetable tissue and are generally obtained by boiling or by extraction under pressure. They are important in the diet (dietary fats) as a source of energy. Energy Homeostasis, minerals Minerals Electrolytes, proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis, or vitamins. Lactose intolerance Lactose intolerance Lactose intolerance (LI) describes a constellation of symptoms due to lactase deficiency (LD), the enzyme located in the brush border of the absorptive cells in the small intestine. Lactose is the disaccharide present in milk and requires hydrolysis by lactase to break it down into its 2 absorbable constituents, glucose and galactose. Lactose intolerance typically presents with bloating, abdominal cramping, diarrhea, and flatulence. Lactose Intolerance and celiac disease Celiac disease Celiac disease (also known as celiac sprue or gluten enteropathy) is an autoimmune reaction to gliadin, which is a component of gluten. Celiac disease is closely associated with HLA-DQ2 and HLA-DQ8. The immune response is localized to the proximal small intestine and causes the characteristic histologic findings of villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. Celiac Disease are related to malabsorption Malabsorption General term for a group of malnutrition syndromes caused by failure of normal intestinal absorption of nutrients. Malabsorption and Maldigestion.
• Failure to thrive Failure to Thrive Failure to thrive (FTT), or faltering growth, describes suboptimal weight gain and growth in children. The majority of cases are due to inadequate caloric intake; however, genetic, infectious, and oncological etiologies are also common. Failure to Thrive: children who are gaining weight or height more slowly compared with other children of similar age or sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria. Usually, they present with underdevelopment of motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology skills gained in early childhood, such as rolling Rolling Movement of tethered, spherical leukocytes along the endothelial surface of the microvasculature. The tethering and rolling involves interaction with selectins and other adhesion molecules in both the endothelium and leukocyte. The rolling leukocyte then becomes activated by chemokines, flattens out, and firmly adheres to the endothelial surface in preparation for transmigration through the interendothelial cell junction. Inflammation over, standing, and walking.
• Dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration: a condition caused by excessive loss of body fluids. Water is lost out of the individual cells of the body, leading to a net decrease in the total volume of water in the body.
• Rectal prolapse Rectal prolapse Rectal prolapse, also known as rectal procidentia, is the protrusion of rectal tissue through the anus. The tissue may include just the mucosa or the full thickness of the rectal wall. Common risk factors include chronic straining, constipation, bowel motility disorders, and weakening of the pelvic floor muscles. Rectal Prolapse: a condition in which the rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal: Anatomy loses its normal attachments inside the body, thereby turning itself inside-out through the anus. Definitive treatment requires surgery.
• Allergic bronchopulmonary aspergillosis Aspergillosis Aspergillosis is an opportunistic fungal infection caused by Aspergillus species, which are common spore-forming molds found in our environment. As Aspergillus species are opportunistic, they cause disease primarily in patients who are immunocompromised. The organs that are most commonly involved are the lungs and sinuses. Aspergillus/Aspergillosis: a hypersensitivity response to the fungus Aspergillus Aspergillus A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family trichocomaceae. Echinocandins. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship most often affected are those with asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma or cystic Cystic Fibrocystic Change fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans.
• Biliary cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis: a chronic disease in which bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy ducts are slowly degraded. With the backup of bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship often suffer from cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis.
• Asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma: a chronic inflammatory condition characterized by reversible obstruction to airflow in the lower airways. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with intermittent or persistent wheezing Wheezing Wheezing is an abnormal breath sound characterized by a whistling noise that can be relatively high-pitched and shrill (more common) or coarse. Wheezing is produced by the movement of air through narrowed or compressed small (intrathoracic) airways. Wheezing, cough, and dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea. Diagnosis is usually confirmed with pulmonary function testing Pulmonary Function Testing Pulmonary Function Tests that shows a reversible obstructive pattern. Treatment varies based on the severity and includes bronchodilators Bronchodilators Asthma Drugs and inhaled corticosteroids Corticosteroids Chorioretinitis for control of inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation.
• Primary ciliary dyskinesia Primary Ciliary Dyskinesia Primary ciliary dyskinesia (PCD), also known as immotile-cilia syndrome, is an autosomal recessive disorder leading to an impairment that affects mucociliary clearance. Primary ciliary dyskinesia is caused by defective ciliary function in the airways and is characterized by the loss of oscillation (immotility), abnormal oscillation (dyskinesia), or absence of cilia (aplasia). Primary Ciliary Dyskinesia ( PCD PCD Primary ciliary dyskinesia (PCD), also known as immotile-cilia syndrome, is an autosomal recessive disorder leading to an impairment that affects mucociliary clearance. Primary ciliary dyskinesia is caused by defective ciliary function in the airways and is characterized by the loss of oscillation (immotility), abnormal oscillation (dyskinesia), or absence of cilia (aplasia). Primary Ciliary Dyskinesia): a rare autosomal-recessive genetic disorder leading to dysfunction of the ciliated epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present early in childhood with recurring rhinosinusitis, otitis, respiratory infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, and eventual bronchiectasis Bronchiectasis Bronchiectasis is a chronic disease of the airways that results from permanent bronchial distortion. This results from a continuous cycle of inflammation, bronchial damage and dilation, impaired clearance of secretions, and recurrent infections. Bronchiectasis. PCD PCD Primary ciliary dyskinesia (PCD), also known as immotile-cilia syndrome, is an autosomal recessive disorder leading to an impairment that affects mucociliary clearance. Primary ciliary dyskinesia is caused by defective ciliary function in the airways and is characterized by the loss of oscillation (immotility), abnormal oscillation (dyskinesia), or absence of cilia (aplasia). Primary Ciliary Dyskinesia is often associated with situs inversus and infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility.