Cystic Fibrosis (Clinical)

Epidemiology

• Synonyms: mucoviscidosis Mucoviscidosis Cystic fibrosis is an autosomal recessive disorder caused by mutations in the gene cftr. The mutations lead to dysfunction of chloride channels, which results in hyperviscous mucus and the accumulation of secretions. Common presentations include chronic respiratory infections, failure to thrive, and pancreatic insufficiency. Cystic Fibrosis, fibrosa cystica Fibrosa cystica Cystic fibrosis is an autosomal recessive disorder caused by mutations in the gene cftr. The mutations lead to dysfunction of chloride channels, which results in hyperviscous mucus and the accumulation of secretions. Common presentations include chronic respiratory infections, failure to thrive, and pancreatic insufficiency. Cystic Fibrosis
• 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:^[2,3]
  • 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^[1–3]

• Autosomal recessive inheritance Autosomal recessive inheritance Autosomal Recessive and Autosomal Dominant 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^[2,3]

• 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 other 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 Chronic Inflammation 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 Chronic Inflammation 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 ducts of the exocrine gland portion
  • 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 Biliary cirrhosis Fibrosis of the hepatic parenchyma due to obstruction of bile flow (cholestasis) in the intrahepatic or extrahepatic bile ducts. Primary biliary cholangitis involves the destruction of small intrahepatic bile ducts and decreased bile secretion. Secondary biliary cholangitis is produced by prolonged obstruction of large intrahepatic or extrahepatic bile ducts from a variety of causes. Cystic Fibrosis
• Intestines:
  • Obstipation Obstipation Large Bowel Obstruction

Clinical Presentation

Respiratory system^[2–4]

• 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 Recurrent pulmonary infections Selective IgA Deficiency, especially with Pseudomonas aeruginosa Pseudomonas aeruginosa A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. Aeruginosa is a major agent of nosocomial infection. Pseudomonas 
  • 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 Expiratory Wheezing Wheezing and barrel chest

Gastrointestinal system^[2–4]

Reproductive system^[2–4]

• 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^[2–4]

• 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 aureus Staphylococcus 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. Brain Abscess 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

Diagnosis relies on clinical signs and symptoms suggestive of CF, as well as objective evidence of CFTR dysfunction (see overview of approach in algorithm below).^[2,3,6,8,10]

Newborn Newborn An infant during the first 28 days after birth. Physical Examination of the Newborn screening Screening Preoperative Care^[8]

• 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.
• Performed before sweat chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes testing because that test is relatively complicated to carry out and must be done in a certified center by experienced operators.

Sweat chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes test: gold standard of diagnosis^[8]

•   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
• < 30 mmol/L: CF unlikely
• 30–59 mmol/L (intermediate sweat chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes level): CFTR gene sequencing Gene sequencing Polymerase Chain Reaction (PCR) is required.

Further testing

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

Nasal potential difference ( NPD NPD Niemann-pick disease (NPD) is a rare, inherited, lysosomal storage disorder. The disease is classified on the basis of the genetic mutation. Type a and type B result from mutations in the smpd-1 gene, resulting in acid sphingomyelinase enzyme deficiency. Type c results from npc1 or npc2 gene mutations, which are needed for intracellular transport of lipids. Niemann-Pick Disease):^[8]

• 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 Anatomy (External & Internal), 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):^[10]

• 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.
• Epithelial ion transport is measured in the biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma specimen after stimulation with chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes secretory agents.
• The amount of residual function in CFTR chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes channels Channels The Cell: Cell Membrane is studied.
• Helpful diagnostically in those with mild CF phenotype Phenotype The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics and equivocal tests

Diagnostic uncertainties and CF-related diseases:

• A definitive diagnosis cannot always be established up front. 
• Phenotypic presentations can vary from mild to severe.
• Infants with positive screen, but uncertain diagnosis are often classified as having CFTR-related disorders:^[8,17]
  • CFTR-related metabolic syndrome Metabolic syndrome Metabolic syndrome is a cluster of conditions that significantly increases the risk for several secondary diseases, notably cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver. In general, it is agreed that hypertension, insulin resistance/hyperglycemia, and hyperlipidemia, along with central obesity, are components of the metabolic syndrome. Metabolic Syndrome (CRMS):
    • ↑ Trypsinogen Trypsinogen The inactive proenzyme of trypsin secreted by the pancreas, activated in the duodenum via cleavage by enteropeptidase. Pancreatic Parameters on newborn Newborn An infant during the first 28 days after birth. Physical Examination of the Newborn screening Screening Preoperative Care
    • Sweat chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes test < 60 mmol/L
    • ≥ 1 CFTR mutations, with ≥ 1 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 not categorized as CF-causing 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
  • CF screen positive, inconclusive diagnosis (CFSPID): newborn Newborn An infant during the first 28 days after birth. Physical Examination of the Newborn screen positive but does not meet criteria for CF

Additional assessment

Order these tests based on presenting signs and symptoms.^[2,18]

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 aeruginosa Pseudomonas aeruginosa A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. Aeruginosa is a major agent of nosocomial infection. Pseudomonas
• Haemophilus influenzae Haemophilus Influenzae A species of Haemophilus found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through viii. Haemophilus, 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

Pulmonary function test Pulmonary function test Pulmonary function tests are a group of diagnostic procedures yielding useful, quantifiable information about the rate of the flow of air through the individual’s airways, lung capacity, and the efficiency of gas exchange in relation to time. The most commonly utilized tests include spirometry (before and after bronchodilator use), lung volumes, and quantitation of diffusing capacity for carbon monoxide (CO). The tests can be influenced by the individual’s effort/fatigue, disease state, or anatomical malformation. Pulmonary Function Tests:^[12]

• Used to assess severity and follow progression of lung disease in CF
• Forced expiratory volume in 1 second (FEV1): single most important predictor of survival in CF
• A rapidly decreasing or persistently low (< 30%) FEV1 is an indication for referral for lung transplantation Lung transplantation The transference of either one or both of the lungs from one human or animal to another. Organ Transplantation.

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.

Overview

Details of respiratory management

Although CF affects multiple organ systems, lung disease remains the leading cause of morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status and mortality Mortality All deaths reported in a given population. Measures of Health Status.

Vaccinations:

• Seasonal influenza Influenza Influenza viruses are members of the Orthomyxoviridae family and the causative organisms of influenza, a highly contagious febrile respiratory disease. There are 3 primary influenza viruses (A, B, and C) and various subtypes, which are classified based on their virulent surface antigens, hemagglutinin (HA) and neuraminidase (NA). Influenza typically presents with a fever, myalgia, headache, and symptoms of an upper respiratory infection. Influenza Viruses/Influenza vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship ≥ 6 months of age
• Pneumococcal vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination
• Coronavirus disease 2019 Coronavirus disease 2019 Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly affects the respiratory system but can also cause damage to other body systems (cardiovascular, gastrointestinal, renal, and central nervous systems). vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination

Early diagnosis and prevention of lung damage:^[9,13]

• Key to prolonged survival
• Start therapies before symptoms develop.
• Strategies delaying progression of pulmonary damage:
  • Physiotherapy Physiotherapy Spinal Stenosis
  • Hypertonic saline Hypertonic saline Hypertonic sodium chloride solution. A solution having an osmotic pressure greater than that of physiologic salt solution (0. 9 g NaCl in 100 ml purified water). Hyponatremia inhalations
  • Pulmozyme (recombinant human DNAse) inhalation
  • Antibiotics
  • Antiinflammatory drugs
• Ensure a smoke-free environment.

Enhancement of 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:^[9,13,18]

• Thick mucus is a nidus for infection.
• Airway Airway ABCDE Assessment clearance techniques (ACTs) and devices:
  • Positive expiratory pressure ( PEP PEP A monocarboxylic acid anion derived from selective deprotonation of the carboxy group of phosphoenolpyruvic acid. It is a metabolic intermediate in glycolysis; gluconeogenesis; and other pathways. Glycolysis) masks
  • Acapella (device combining PEP PEP A monocarboxylic acid anion derived from selective deprotonation of the carboxy group of phosphoenolpyruvic acid. It is a metabolic intermediate in glycolysis; gluconeogenesis; and other pathways. Glycolysis and vibration Vibration A continuing periodic change in displacement with respect to a fixed reference. Neurological Examination)
  • Flutter (pipe-shaped mucus clearance device)
  • High-frequency chest-wall oscillation devices
  • Active cycle of breathing techniques
  • Autogenic drainage
  • Aerobic exercise (beneficial for airway Airway ABCDE Assessment clearance) 
• Bronchodilator (inhaled β-2-adrenergic receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors agonists) therapy:
  • Use prior to chest physiotherapy Physiotherapy Spinal Stenosis and exercise.
  • Use if airway Airway ABCDE Assessment hyperreactivity is present.
• Mucolytics:
  • Pulmozyme (2.5 mg daily)
  • Hyperosmolar agents ( hypertonic saline Hypertonic saline Hypertonic sodium chloride solution. A solution having an osmotic pressure greater than that of physiologic salt solution (0. 9 g NaCl in 100 ml purified water). Hyponatremia inhalation 4 ml twice daily with  bronchodilator treatment given previously)

Managing Pseudomonas aeruginosa Pseudomonas aeruginosa A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. Aeruginosa is a major agent of nosocomial infection. Pseudomonas 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:^[9,13,15]

• P. aeruginosa P. aeruginosa A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. Aeruginosa is a major agent of nosocomial infection. Pseudomonas 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 are associated with:
  • ↓ Pulmonary function
  • ↓ Nutrition
  • ↓ 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
  • ↑ Hospital admissions
• Prevention of colonization Colonization Bacteriology:
  • P. aeruginosa P. aeruginosa A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. Aeruginosa is a major agent of nosocomial infection. Pseudomonas 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 are the leading cause of morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status and mortality Mortality All deaths reported in a given population. Measures of Health Status.
  • Routine oropharyngeal cultures are recommended.
  • Early initiation of antipseudomonal antibiotics can clear initial infection and prevent chronic colonization Colonization Bacteriology.
  • Inhaled tobramycin 300 mg twice a day for 28 days is beneficial in treating initial or new P. aeruginosa P. aeruginosa A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. Aeruginosa is a major agent of nosocomial infection. Pseudomonas infection.^[18]
• Suppression Suppression Defense Mechanisms of chronic 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 colonization Colonization Bacteriology:
  • Chronic colonization Colonization Bacteriology:
    • Associated with more rapid decline of lung function
    • Mostly caused by biofilm-forming strains resistant to antibiotics
  • Inhaled tobramycin 300 mg twice a day is an effective strategy that shows sustained improvements in lung function.
  • Azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides 10 mg/kg (maximum, 500 mg/dose) 3 times a week is also recommended for those with cultures persistently positive for P. aeruginosa P. aeruginosa A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. Aeruginosa is a major agent of nosocomial infection. Pseudomonas.
    • Chronic use in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with occult or active nontuberculous mycobacteria Mycobacteria Mycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections. Mycobacterium (NTM) infection could lead to resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing.
    • Screen patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship for NTM first (before starting azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides); reassessment is advised every 6–12 months.
  • Inhaled tobramycin + azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides as part of eradicating 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 decreased pulmonary exacerbations.^[15]
  • Inhaled aztreonam Aztreonam The carbapenems and aztreonam are both members of the bactericidal beta-lactam family of antibiotics (similar to penicillins). They work by preventing bacteria from producing their cell wall, ultimately leading to bacterial cell death. Carbapenems and Aztreonam is another option for those with persistently positive P. aeruginosa P. aeruginosa A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. Aeruginosa is a major agent of nosocomial infection. Pseudomonas cultures to improve lung function.
• Other chronic 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/colonizations that can affect lung function:
  • 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, nontuberculous mycobacteria Mycobacteria Mycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections. Mycobacterium
  • Methicillin-resistant Staphylococcus aureus Staphylococcus 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. Brain Abscess (CF Foundation does not recommend oral anti-staphylococcal antibiotics).

Treatment of acute pulmonary exacerbations:^[15,16]

• Acute worsening of pulmonary function that may manifest with ≥ 1 of the following:
  • New or increased coughing or sputum production
  • Increased 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
  • Increased fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
  • Increased nasal congestion
  • Decreased appetite or weight
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
• Most exacerbations are not due to acquired new strains of pathogens, but are likely due to a clonal expansion Clonal Expansion Seborrheic Keratosis of existing strains.
• Intervention should be early and aggressive, as irreversible decline in lung function may occur.
  • Includes intensification of ACT techniques and antibiotics based on sputum cultures
  • Antibiotic combinations are used (with no specific combination recommended over another):
    • At least 1 antibiotic covering each organism in cultures
    • And traditionally, 2 antibiotics are used against P. aeruginosa P. aeruginosa A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. Aeruginosa is a major agent of nosocomial infection. Pseudomonas.
    • Duration ranges from 10 to 21 days.
• General goals in treating exacerbations:
  • Improved FEV1
  • Improved symptoms

Treatment of airway Airway ABCDE Assessment 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:^[9,13,18]

• Azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides:
  • Possesses antibacterial Antibacterial Penicillins effect as well as suppressive effect on inflammatory response
  • Given 3 times weekly (250 mg if < 36 kg; 500 mg if > 36 kg)
• High-dose ibuprofen Ibuprofen A nonsteroidal anti-inflammatory agent with analgesic properties used in the treatment of rheumatism and arthritis. Nonsteroidal Antiinflammatory Drugs (NSAIDs) (25 mg/kg/dose) twice daily (for those 6–17 years of age, with an FEV1 ≥ 60%)
• Inhaled corticosteroid use is controversial; can be used for 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 in the setting of CF.
• Routine use of oral glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids is not recommended.

Treatment of allergic bronchopulmonary aspergillosis Allergic bronchopulmonary aspergillosis Hypersensitivity reaction (allergic reaction) to fungus aspergillus in an individual with long-standing bronchial asthma. It is characterized by pulmonary infiltrates, eosinophilia, elevated serum immunoglobulin e, and skin reactivity to aspergillus antigen. Aspergillus/Aspergillosis ( ABPA ABPA Hypersensitivity reaction (allergic reaction) to fungus aspergillus in an individual with long-standing bronchial asthma. It is characterized by pulmonary infiltrates, eosinophilia, elevated serum immunoglobulin e, and skin reactivity to aspergillus antigen. Aspergillus/Aspergillosis):^[9]

• Allergic response to respiratory colonization Colonization Bacteriology with Aspergillus Aspergillus A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family trichocomaceae. Echinocandins fumigatus, manifesting with:
  • 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
  • Pulmonary infiltrates
  • 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
  • Fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans
• Need to treat, as ABPA ABPA Hypersensitivity reaction (allergic reaction) to fungus aspergillus in an individual with long-standing bronchial asthma. It is characterized by pulmonary infiltrates, eosinophilia, elevated serum immunoglobulin e, and skin reactivity to aspergillus antigen. Aspergillus/Aspergillosis may quickly progress to severe fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans
• Diagnosis is difficult, as many symptoms overlap with CF itself. 
• The following minimal criteria for diagnosis are:^[9,18] 
  • Predisposing conditions (≥ 1 of the following):
    • 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
    • CF
  • With both of the following present:
    • ↑ Total serum IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions concentration (> 500 IU/mL)
    • Immediate cutaneous reactivity to Aspergillus Aspergillus A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family trichocomaceae. Echinocandins species OR ↑ serum IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions to A. fumigatus A. fumigatus A species of imperfect fungi from which the antibiotic fumigatin is obtained. Its spores may cause respiratory infection in birds and mammals. Aspergillus/Aspergillosis 
  • Supporting criteria (≥ 2 of the following):
    • IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis to A. fumigatus A. fumigatus A species of imperfect fungi from which the antibiotic fumigatin is obtained. Its spores may cause respiratory infection in birds and mammals. Aspergillus/Aspergillosis
    • Central 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 (on CT) or pulmonary infiltrates or mucus plugging (on chest radiography)
    • Peripheral blood eosinophilia Eosinophilia Abnormal increase of eosinophils in the blood, tissues or organs. Autosomal Dominant Hyperimmunoglobulin E Syndrome (> 500 cells/µL)
• Perform screening Screening Preoperative Care:^[18] 
  • Obtain total serum IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions concentration annually.
  • If > 500 IU/mL, proceed with immediate cutaneous reactivity to A. fumigatus A. fumigatus A species of imperfect fungi from which the antibiotic fumigatin is obtained. Its spores may cause respiratory infection in birds and mammals. Aspergillus/Aspergillosis or an in vitro test for IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions antibody to A. fumigatus A. fumigatus A species of imperfect fungi from which the antibiotic fumigatin is obtained. Its spores may cause respiratory infection in birds and mammals. Aspergillus/Aspergillosis.
  • If level is 200–500 IU/mL, repeat testing in 1–3 months.
  • Positive result → treat
• Treatment is systemic steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors (1st-line).

Use of CFTR modulators:^[14,19]

• This class of drugs improves the production, processing, and function of the CFTR protein.
• Associated with improved lung function and quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of life and reduction of exacerbations.
• Available options:
  • Ivacaftor:
    • 150 mg every 12 hours (ages ≥ 6 years; lower dose for younger patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with ages ≥ 4 months)
    • For patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with ≥ 1 G551D CFTR 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 
  • Tezacaftor 100 mg /ivacaftor 150 mg (dual combination):
    • 1 combination tablet in the morning, 1 ivacaftor tablet in the evening (12 hours apart)
    • For patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship ages ≥ 6 years with 2 copies of the F508del 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 or at least a CFTR 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 that is responsive based on data
  • Lumacaftor 200 mg/ivacaftor 125 mg (dual combination):
    • 2 tablets twice a day
    • For patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship ages ≥ 1 year with 2 copies of the F508del 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
  • Elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg (triple combination):
    • 2 tablets in the morning, 1 in the evening
    • For patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship ages ≥ 2 years with at ≥ 1 copy of the F508del 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 or at least a CFTR 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 that is responsive based on data

Referral to transplant center:^[2,11,18]

• Previously thought of as “last resort” but now recommended earlier in disease course if with:
  • Rapid decline in FEV1
  • Hypoxia Hypoxia Sub-optimal oxygen levels in the ambient air of living organisms. Ischemic Cell Damage (rest or exertion)
  • Hypercarbia (PCO₂ > 50 on ABG testing)
  • 6-minute walk test (6MWT) distance < 400 m
  • Significant pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension
  • Exacerbation needing positive pressure ventilation Positive pressure ventilation Application of positive pressure to the inspiratory phase when the patient has an artificial airway in place and is connected to a ventilator. Flail Chest
• Studies show excellent short- and long-term outcomes.
• Survival is worse for pediatric patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship, patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with B. cepacia, and patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship undergoing repeat transplantation.

Additional management^[9,18]

• Nutrition:
  • Individual regimen, with monitoring of growth and body mass index Body mass index An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity
  • Supplementation with vitamins A, D, E, and K (fat-soluble vitamins)
  • Diets rich in essential fatty acids Essential fatty acids Long chain organic acid molecules that must be obtained from the diet. Examples are linoleic acids and linolenic acids. Fatty Acids and Lipids
• 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 supplementation is given, especially in predisposing climate conditions (e.g., hot environments).
• Pancreatic function:
  • Pancreatic enzyme replacement Enzyme replacement Therapeutic replacement or supplementation of defective or missing enzymes to alleviate the effects of enzyme deficiency (e.g., glucosylceramidase replacement for gaucher disease). Severe Combined Immunodeficiency (SCID) should be started in those with 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 < 200 μg/g.
  • Medications are given at the beginning of meals, and units of lipase Lipase An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. Malabsorption and Maldigestion are based on patient weight or the fat ingested.
• Screen for CF-related conditions:
  • Screen for diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus starting at ≥ 10 years of age
  • Screen for bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types disease using dual X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests absorptiometry (DXA) scan on all adults and children > 8 years if < 90% ideal body weight
  • Those who are pancreatic-sufficient should be screened annually for pancreatic insufficiency.
  • Screen for 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 disease by:
    • Physical exam (look for findings such as hepatosplenomegaly Hepatosplenomegaly Cytomegalovirus, ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites); suspicion should lead to:
      • Annual laboratory tests (e.g., AST AST Enzymes of the transferase class that catalyze the conversion of l-aspartate and 2-ketoglutarate to oxaloacetate and l-glutamate. Liver Function Tests, ALT ALT An enzyme that catalyzes the conversion of l-alanine and 2-oxoglutarate to pyruvate and l-glutamate. Liver Function Tests, gamma glutamyl transferase Gamma glutamyl transferase An enzyme, sometimes called ggt, with a key role in the synthesis and degradation of glutathione; (GSH, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid. Alcoholic Liver Disease ( GGT GGT An enzyme, sometimes called ggt, with a key role in the synthesis and degradation of glutathione; (gsh, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid. Alcoholic Liver Disease), albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests, prothrombin time Prothrombin time Clotting time of plasma recalcified in the presence of excess tissue thromboplastin. Factors measured are fibrinogen; prothrombin; factor V; factor VII; and factor X. Hemostasis)
  • Screen for depression and anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder:
    • Clinically assess for presence of depression and anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder in children ages 7–11 years.
    • Annual screening Screening Preoperative Care for all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship ≥ 12 years of age

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.^[2]
• 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: less favorable
  • 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 usually occur independently, but most of them may also be associated with 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 bronchial walls thicken and the airways dilate 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. 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 Chronic Inflammation 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 Allergic bronchopulmonary aspergillosis Hypersensitivity reaction (allergic reaction) to fungus aspergillus in an individual with long-standing bronchial asthma. It is characterized by pulmonary infiltrates, eosinophilia, elevated serum immunoglobulin e, and skin reactivity to aspergillus antigen. 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 Biliary cirrhosis Fibrosis of the hepatic parenchyma due to obstruction of bile flow (cholestasis) in the intrahepatic or extrahepatic bile ducts. Primary biliary cholangitis involves the destruction of small intrahepatic bile ducts and decreased bile secretion. Secondary biliary cholangitis is produced by prolonged obstruction of large intrahepatic or extrahepatic bile ducts from a variety of causes. Cystic Fibrosis: 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 Ciliary dyskinesia 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.