People have the right to be involved in discussions and make informed decisions about their care, as described in your care. Making decisions using NICE guidelines explains how we use words to show the strength or certainty of our recommendations, and has information about prescribing medicines including off-label use , professional guidelines, standards and laws including on consent and mental capacity , and safeguarding. Mannitol dry powder for inhalation for treating cystic fibrosis NICE technology appraisal guidance Colistimethate sodium and tobramycin dry powders for inhalation for treating pseudomonas lung infection in cystic fibrosis NICE technology appraisal guidance Avoid jargon and use formats that they prefer, for example:.
Additional or alternative mutations present at significant frequencies in an Cystic fibrosis screening protocol for adults population served by an NBS program may be added. Corresponding author. Saiman, J. Cause a change in amino acid sequence that severely affects CFTR synthesis or function; or. Multiple-breath washout as a lung function test in cystic fibrosis. Solis-Moya, L. Palabras clave:. For example, the age of onset of symptoms is increasingly recognized as being highly variable, ranging from prenatal evidence of echogenic bowel to onset of symptoms in late adolescence or adulthood that nevertheless can cause major morbidity and premature mortality. Elkins, M.
Siamese twins freeks. Subscribe to our newsletter
Infants with intermediate sweat chloride values and no or 1 CF-causing mutation cannot be diagnosed definitively with CF. Uncertainty in the diagnosis of cystic fibrosis: possible role of in vivo nasal potential difference measurements. Frank J. Although the risk Cystic fibrosis screening protocol for adults poor outcomes should be weighed against the psychosocial risks of assigning a CF diagnosis, 6162 infants with a known CF-causing mutation Table II and Cystic fibrosis screening protocol for adults 7T are at sufficiently high risk for lung disease to merit clinical monitoring in a CF care center. Assessments may include the following: Fubrosis assessment, including anthropometrics, growth, and state of the lungs Personal prootocol history Family zdults of CF and related phenotypes Extended genetic testing, if required Pancreatic function tests Oropharyngeal culture for CF-associated pathogens, especially Pseudomonas aeruginosa Chest radiograph Liver function tests. Cystic fibrosis care at Mayo Clinic. LeGrys Screening. Because nutrition is so important to a long and high-quality of life for people with CF, the CF Foundation has created several clinical care guidelines related to nutritional Pubescent genitals photos gastrointestinal GI issues. In the absence of 2 CF-causing mutations, sweat chloride testing should be repeated to ensure a correct diagnosis. To ensure that people with CF continue to experience steady gains in length and quality of life, the Foundation helps its accredited care centers provide a standard of CF care with guidelines. Rosenstein B, Cutting G. Such widespread NBS is rapidly changing the diagnostic paradigm. Screenjng secreted fluids are normally thin and slippery.
To ensure that people with CF continue to experience steady gains in length and quality of life, the Foundation helps its accredited care centers provide a standard of CF care with guidelines.
- Jump to content.
The Spanish Association of Pediatrics has as one of its main objectives the dissemination of rigorous and updated scientific information on the different areas of pediatrics. Annals of Pediatrics is the Body of Scientific Expression of the Association and is the vehicle through which members communicate. The Impact Factor measures the average number of citations received in a particular year by papers published in the journal during the two receding years. CiteScore measures average citations received per document published.
SRJ is a prestige metric based on the idea that not all citations are the same. SJR uses a similar algorithm as the Google page rank; it provides a quantitative and qualitative measure of the journal's impact. SNIP measures contextual citation impact by wighting citations based on the total number of citations in a subject field. Newborn screening NBS for cystic fibrosis CF is well-established in many countries and provides the opportunity for an early diagnosis and treatment before the development of irreversible structural lung damage..
In the last 10 years its implementation rapidly spread and all the autonomies offer the NBS programme for CF since There are many different strategies across Spain. It is believed that it is very opportune to have an updated and consensual guide for the diagnosis, follow-up, and treatment of patients diagnosed by neonatal screening.. In , the Canadian Cystic Fibrosis Foundation reported a median survival of Cystic fibrosis meets the criteria warranting early detection and NS for the purpose of determining the actual incidence of the disease, early genetic counselling and immediate initiation of treatment with the purpose of preventing or minimising lung damage, as molecules that can target and correct the defect in the abnormal cystic fibrosis transmembrane conductance regulator CFTR protein are currently available..
Since , neonatal screening is performed in every autonomous community in Spain.. We think it would be very convenient to have an updated consensus-based guideline for the diagnosis of CF and the follow-up and treatment of patients that meet the diagnostic criteria. This document summarises all the multidisciplinary aspects involved in the management of these patients.. Serum levels of immunoreactive trypsinogen IRT are higher in newborns with CF and remain elevated longer compared to newborns who are not affected by the disease.
An elevation of IRT at birth is not specific for CF, as there are healthy newborns that experience a transient elevation of this enzyme. Protocols for diagnosis of cystic fibrosis through neonatal screening proposed by the European Best Practice Guidelines for Cystic Fibrosis Neonatal Screening 7 applied in Spain.. In each population, the applied protocol should be adapted to its mutation spectrum..
There are 4 possible outcomes of genetic testing in a newborn with elevated IRT: a If the test detects 2 CF-causing mutations, the newborn should undergo a sweat test and DNA segregation analysis should be performed to confirm that each mutation comes from a different parent.. In case of a single mutation, a sweat test should be performed. If the sweat test is negative, the newborn is considered a carrier.. Cases where no mutation is found and the sweat test is normal are considered false positives of screening..
There is another group comprising those newborns in whom a conclusive diagnosis cannot be made, even with use of ancillary tests, for which the Working Group on CF of the European Cystic Fibrosis Society has proposed the label cystic fibrosis screen positive, inconclusive diagnosis CFSPID. This group of patients requires ongoing follow-up, as in some cases CF is diagnosed at a later age due to onset of symptoms with elevation of sweat chloride levels..
The sweat test is the cornerstone of diagnosis of CF. Newborns with a positive neonatal screen test for CF must be referred for a sweat test exclusively to specialised CF units accredited for diagnosis..
The diagnosis cannot be confirmed based exclusively on the sweat conductivity measurements obtained by the nanoduc t or sweat check systems Macroduct. Samples must be analysed as soon as they are collected.. Patients with persistent intermediate values should undergo a diagnostic evaluation, including extended DNA testing and repetition of the sweat test at 6 months..
Neonatal screening elicits a varying degree of anxiety in parents. If the newborn has CF, parents will be given information on all the tests performed to diagnose the disease and of the encouraging outcomes of new treatments and the extensive research that is underway, thanks to which it is now possible to have an optimistic perspective on the disease..
At the end of the visit, if the newborn is not affected, parents will receive a report stating that the child does not have CF or that the child is a carrier and offering genetic counselling to the parents. For this reason, the psychosocial impact on the family of the new diagnosis must be managed with care.
Manage the expectations of the family.. One of the key goals of the visit is to provide basic information in a positive light with a sensitive and empathic attitude and using simple language. Table 1 specifies the actions to be taken during the first visit.. C, consider performing in this visit; LFT, lung function test; PERT, pancreatic enzyme replacement therapy; V, perform in any of these visits; X, perform in this visit.. Day of diagnosis sweat test and new appointment 24—48 h from diagnosis..
Checkup 1 week after diagnosis or at age approximately 1 month.. Explain how it was determined that the child has CF and provide details regarding the diagnosis, genetics and impact on other siblings and family members.. Train on techniques that facilitate mucociliary clearance: percussion and postural drainage. Coordination with routine primary care visits. Include vaccination against varicella, S. If PI is not present at the time of diagnosis, repeat the faecal elastase test at least twice in the first year of life and annually thereafter, as PI may develop at a later time..
Expiratory CT scan with low-dose radiation and expiratory views to assess peripheral airway disease.. Repeat at 1—2 months from initiation of supplementation. Complete blood count, electrolytes, urea, creatinine, albumin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, bilirubin, alkaline phosphatase.. Lung function tests in infants: consider performance if available in facility.. Obtained informed consent to include child in CF register..
Source : Adapted from Borowitz et al. If the patient is in good condition, subsequent visits may be held at 2- to 3-month intervals.. The main goal of nutritional interventions in CF is to promote normal growth and development for age Table Guide for prescription of nutritional interventions We recommend encouraging breastfeeding on demand.
Whatever the feeding modality, patients with pancreatic insufficiency PI will receive pancreatic enzymes. The introduction of complementary foods should conform to the guidelines for the general population, starting at age 6 months in exclusively breastfed infants and at age 4 to 6 months in formula-fed infants.
As early as the neonatal period, children with CF may exhibit hypovitaminosis and PI.. Recommendations for pancreatic enzyme replacement therapy in children with pancreatic insufficiency.. Different enzyme formulations are currently available Table 4. Pancreatic enzymes should be taken with every meal. Enzyme replacement formulations currently available in Spain.. Based on the recommendations of the European Cystic Fibrosis Society. These patients can experience liver impairment of a heterogeneous nature Table Liver involvement in cystic fibrosis..
It is important to remember sodium chloride supplementation in hot weather.. The dehydrated secretions of these patients hinder mucociliary clearance, giving rise to a vicious cycle of inflammation and chronic lung infection, which calls for early initiation of chest physical therapy. The evidence currently available is insufficient to establish which method is best..
Treatment with recombinant human DNase reduces the viscosity of the mucus and facilitates mucociliary clearance. Hypertonic saline solution has an osmotic effect that restores fluid to the airway surfaces.
Azithromycin modulates cytokine production and plays an indirect role in biofilm formation. In cases where it is indicated for instance, with persistent detection of Pseudomonas in culture , it should be given 3 times a week at the usual dose while monitoring liver function, taking into account that co-administration with inhaled tobramycin could impair the response to the latter.
Neonatal screening for CF provides an opportunity to educate the family and the child from a young age on the importance of hand hygiene in the household. The presence of viscous secretions in the airways characteristic of these patients facilitates recurrent infections by different microorganisms. A Methicillin-sensitive S. The current evidence is insufficient to recommend or discourage eradication of S.
Antibiotic agents used in the management of respiratory disease in cystic fibrosis.. B Methicillin-resistant S. In case of chronic infection, one possible option is inhaled vancomycin for 2—3 weeks.. Treatment for eradication must be initiated as soon as P. None of the eradication protocols published to date has proven superior to the others.
Based on the Spanish consensus guidelines, the management of a first episode with isolation of P. If the culture is negative, we recommend maintenance of daily colistin for a maximum of 3—6 months or 1—3 on—off cycles of tobramycin or aztreonam maximum 6 months.. A consensus definition of pulmonary exacerbation in infants and preschool-aged children with CF is necessary. Some groups have defined it as any change in the usual respiratory symptoms.. If there is no improvement despite adequate treatment, it is possible that the infection is caused by microorganisms resistant to the prescribed antibiotics in this case, assess the need for flexible bronchoscopy and bronchoalveolar lavage , or that other diseases are at play, such as gastro-oesophageal reflux, swallowing problems, etc.
Treatments are currently available that target the underlying defect that causes the disease. In Spain, its used is approved starting at age 6 years, and in the United States starting at 12 months.. It is authorised for use starting at age 2 years in the United States, but is not yet available in Spain..
Should there be any changes in symptoms suggestive of a pulmonary exacerbation, the care team should facilitate performance of a respiratory culture and determine whether empirical antibiotherapy is indicated. The forced expiratory volume in 1 second FEV 1 is useful to define the presence of an exacerbation and the response to treatment. However, there is evidence that even in the presence of structural abnormalities, lung function may be normal in preschool-aged children..
The lung clearance index is a new and very sensitive test that detects abnormalities earlier than spirometry and can be used to assess ventilation inhomogeneity. Neonatal screening for CF offers a unique opportunity for early diagnosis that has been proven to improve nutritional status, lung function and survival and to reduce hospital admissions, all of which may reduce health care costs.
It is widely implemented worldwide and in Spain. Screening can only have beneficial effects if it is followed by strict adherence to the established standards of care, which is why we thought it was essential to publish these guidelines for the diagnosis and follow-up of patients with CF identified through neonatal screening.. The authors have no conflicts of interest to declare.. An Pediatr Barc.
Centers for Disease Control and Prevention. Although women with cystic fibrosis may be less fertile than other women, it's possible for them to conceive and to have successful pregnancies. Document CA2. In: Rossi E, Stoll E, editors. About Us News Blog Chapters. We also use non-essential cookies to help us improve government digital services.
Cystic fibrosis screening protocol for adults. Other UMHS Sites
Cystic fibrosis is an inherited chronic disorder that causes mucus in the body to become thick and sticky. This glue-like mucus builds up and causes problems in many of the body's organs, especially the lungs, which can lead to infections, and the pancreas, making it difficult to properly digest food. While cystic fibrosis is usually diagnosed in childhood, adults with no symptoms or mild symptoms during their youth can still be found to have the disease.
Supporting patients over 21 years of age, our long-established program has also received Quality Improvement Awards from the Cystic Fibrosis Foundation for sustaining quality improvement work that led to better health outcomes for people with cystic fibrosis.
There is no cure for cystic fibrosis, and the disease generally gets worse over time. However, thanks to screening for early diagnosis and new treatments, people with cystic fibrosis—about 30, in the U. S—can live into their 40s and longer. To diagnose cystic fibrosis in adults, we perform a comprehensive exam and collect a thorough history.
A genetics test can also be used to diagnose. Other tests may be required, including a blood test, sputum mucus test, and a lung function test to measure how well you are breathing. These guidelines were created to help care center teams to integrate screening and treating depression and anxiety into comprehensive cystic fibrosis care. To aid clinicians, patients, and families in the best use of modulators, the Cystic Fibrosis Foundation sponsored the creation of guidelines to inform discussions and support decision-making.
Sign up for our emails. Skip to Main Content Skip to Footer. CFF Homepage. About Us News Blog Chapters. Care Clinical Care Guidelines To ensure that people with CF continue to experience steady gains in length and quality of life, the Foundation helps its accredited care centers provide a standard of CF care with guidelines. Cystic Fibrosis Foundation Montgomery Ave.
We will not rest until we find a cure.
Newborn screening NBS for cystic fibrosis CF is increasingly being implemented and is soon likely to be in use throughout the United States, because early detection permits access to specialized medical care and improves outcomes. The diagnosis of CF is not always straightforward, however. The sweat chloride test remains the gold standard for CF diagnosis but does not always give a clear answer. Harmful mutations in the gene can present as a spectrum of pathology ranging from sinusitis in adulthood to severe lung, pancreatic, or liver disease in infancy.
Thus, CF identified postnatally must remain a clinical diagnosis. Their recommendations, presented herein, involve a combination of clinical presentation, laboratory testing, and genetics to confirm a diagnosis of CF. Persistent chest radiograph abnormalities eg, bronchiectasis, atelectasis, infiltrates, hyperinflation. Pancreatic: PI, recurrent acute pancreatitis, chronic pancreatitis, pancreatic abnormalities on imaging. Hepatic: prolonged neonatal jaundice, chronic hepatic disease manifested by clinical or histological evidence of focal biliary cirrhosis or multilobular cirrhosis.
Nutritional: failure to thrive protein-calorie malnutrition , hypoproteinemia and edema, complications secondary to fat-soluble vitamin deficiencies. Modified from Rosenstein B, Cutting G.
The diagnosis of cystic fibrosis: a consensus statement. Cystic Fibrosis Foundation Consensus Panel. J Pediatr ;— Used with permission. The significant advances in the diagnosis and treatment of CF over the past decade have increased our understanding of the disease, making this an opportune time to reexamine the criteria for a diagnosis of CF.
For example, the age of onset of symptoms is increasingly recognized as being highly variable, ranging from prenatal evidence of echogenic bowel to onset of symptoms in late adolescence or adulthood that nevertheless can cause major morbidity and premature mortality. Our knowledge of the scope and complexity of CFTR gene mutations also has expanded greatly. In , approximately mutations had been identified, with typical commercial panels screening for only 30 of them. Extensive genetic studies have produced both greater awareness of the spectrum of mutations in specific population groups 13 and increased understanding of genotype—phenotype relationships, 14 , 15 illuminating distinctions between CFTR mutations with limited or no functional effects and those known or predicted to cause CF disease.
One of the greatest changes over the past decade has been the way in which individuals with CF come to recognition. Such widespread NBS is rapidly changing the diagnostic paradigm.
In contrast to individuals who are diagnosed due to clinical features suggestive of CF, infants referred for diagnostic testing after a positive screen, though they may be underweight, 18 often have no clear clinical manifestations of the disease. Because normal IRT reference values vary slightly, the individual NBS program in the state in which the newborn is being tested sets the specific cutoff value that defines an elevated IRT. A positive screening result, indicating persistent hypertrypsinogenemia, must be followed by referral for direct diagnostic testing ie, sweat chloride test to confirm a diagnosis of CF.
Although such infants represent only a small fraction of patients, they may be at risk for developing complications of CF and thus should be identified and followed. The opportunity provided by NBS to diagnose individuals before symptoms appear and the ability to apply recently acquired knowledge of CF genotype and phenotype relationships to the diagnostic process clearly demonstrate the need for an improved algorithm for diagnosis.
Toward this end, in the Cystic Fibrosis Foundation convened another diagnosis consensus committee of experts, including some members of the panel from together with representatives from the United States, Canada, Europe, and Australia. In addition to addressing the needs of the clinician faced with the infant with a positive screen, the meeting also provided an opportunity to apply the newly acquired tools to older patients with diagnostic uncertainty.
This article presents consensus recommendations for a diagnosis of CF developed by the committee after reviewing recent data, including a diagnostic algorithm formulated by an international group of experts following a European consensus conference. In the end, the diagnosis of CF must be based on good clinical judgment and, in rare cases, may become apparent only over time. The measurement of sweat electrolyte concentrations has been the mainstay of diagnosing CF since a standardized procedure, known as the Gibson-Cooke method, was established in Although the ability to test for CFTR gene mutations gives a new dimension to diagnosing CF, the sweat chloride test remains the standard procedure to confirm a CF diagnosis.
Appropriate performance of the sweat test is crucial for the accurate diagnosis of CF. Details on performing the sweat test can be found in the aforementioned documents. Some data suggest that infants under age 3 months may be at greater risk for insufficient sweat volume collection, 30 but this issue requires further investigation with different sweat collection methods before a standard recommendation can be established.
Factors that influence sweat volume include age, sex, body weight, race, condition of the skin, and collection system used. The sensitivity of chloride detection should be validated by the laboratory. Sweat conductivity or osmolality should not be used for diagnosing CF at the present time.
Bilateral testing is suggested as a useful means of ensuring that at least 1 adequate sweat sample is obtained although inadequate samples from 2 sites should never be pooled for analysis. The analysis of 2 separate samples from bilateral collection also could increase the reliability of the result, although it does not provide a substitute for a second sweat test, which is required sometimes.
Standard procedure should be to perform the analysis within a few hours after collection. Validation of storage is especially important when the Macroduct system is used, because the stability of sweat collected in Macroduct coils has not yet been established.
This classification of sweat chloride ranges was initially affirmed through an examination of sweat tests performed between and Although such traditionally accepted sweat chloride ranges appear to be adequate for diagnosing CF in children presenting with pancreatic exocrine insufficiency and suppurative lung disease, an increasing number of children are being identified as being at risk for CF in other ways.
Studies of sweat chloride testing in infants have demonstrated that the age at which testing is done is an important consideration when interpreting the sweat chloride value. In a small number of individuals, sweat chloride values remain inconclusive for months or even years.
This indicates that repeat sweat testing is sometimes a necessary component of accurate diagnosis. Reference values for sweat chloride in the first 3 months of life have largely been determined from a detailed study of infants identified as being at risk through NBS or based on clinical presentation who carried 0, 1, or 2 copies of the common CFTR gene mutation Fdel.
Although no systematic follow-up of these infants was conducted to determine whether any could be diagnosed with CF, no cases of CF emerged from this cohort in the subsequent 10 years.
The findings from this study have been supported by similar findings in studies from Australia 41 and Massachusetts. In addition to the burgeoning group of infants identified as at risk for CF through NBS, increasing recognition of the great variations in symptomatology of the disease is increasing the numbers of older children, adolescents, and adults in whom the diagnosis is being considered, including many with an indistinct CF phenotype.
Clear sweat chloride reference intervals are required, but studies of normal sweat chloride values beyond infancy using current standardized testing procedures remain limited. These findings suggest that sweat chloride analysis alone may not be used to diagnose CF. Clinical follow-up should occur at 6-to month intervals, and repeat sweat chloride testing should be performed periodically, particularly if a change in symptoms occurs, until the diagnosis is clear.
For the vast majority of persons with CF, the sweat chloride test remains the best diagnostic indicator. For those individuals with sweat chloride values in the intermediate range, DNA analysis can help establish the diagnosis. The latter situation is not generally associated with disease. Despite the potential usefulness of the information, acquiring a CF genotype can be difficult.
Even if the genotype is identified, the consequences of the vast majority of CFTR mutations remain unknown. A mutation is simply a change from the accepted normal sequence of the gene and its control elements. To be considered a cause of CF, the mutation must:. Cause a change in amino acid sequence that severely affects CFTR synthesis or function; or. The Cystic Fibrosis Foundation is considering the feasibility of characterizing these CFTR mutations to determine the molecular basis for their effects on cell function.
The knowledge gained should help scientists determine the usefulness of new targeted therapies that may potentiate channel performance or correct protein trafficking in individuals carrying these mutations, as well as aid diagnosis. As our understanding of the effects of different CFTR mutations develops, the list of mutations that provide acceptable diagnostic evidence will need to be expanded.
In the meantime, extensive genetic analysis to identify large deletions or other obviously destructive mutations may be useful in resolving the diagnosis in individual cases. Additional or alternative mutations present at significant frequencies in an ethnic population served by an NBS program may be added. Because the effects of many mutations remain obscure, and because some allow pancreatic sufficiency PS due to a slight degree of residual chloride channel function, some individuals with these mutations can remain undiagnosed until adulthood.
It may be difficult to distinguish these individuals from those with disease in single organs eg, congenital absence of the vas deferens, idiopathic pancreatitis, various sinopulmonary disorders , who carry a higher frequency of CFTR gene mutations than the general population. The likelihood of CF in this group is driven by the length of a polythymidine tract in intron 8 of the RH allele.
Thus, RH 7T is a mutation that when present in trans with a CF-causing mutation, can cause a variable phenotype, ranging from normal to CF. Although the risk of poor outcomes should be weighed against the psychosocial risks of assigning a CF diagnosis, 61 , 62 infants with a known CF-causing mutation Table II and RH 7T are at sufficiently high risk for lung disease to merit clinical monitoring in a CF care center.
Some individuals with mutations in both copies of the CFTR gene who have partial phenotypes, designated CFTR-related disorders, eventually may receive a diagnosis of CF based on current diagnostic criteria.
In others, a very mild or single system phenotype may allow definitive exclusion of the diagnosis. In effect, as knowledge of the range of phenotypes associated with CFTR gene mutations has expanded, the demarcation line between patients with CF disease and those with disorders associated with CFTR mutations has blurred.
Thus, in this clinical setting, CF cannot be diagnosed simply by the presence of 2 CFTR mutations; these 2 mutations must cause significant loss of function to result in a CF clinical phenotype. Regardless of the types of mutations found, with the possible exception of male infertility, genotype analysis cannot be used to predict prognosis in individual patients with CF.
Even individuals carrying identical Fdel mutations on both alleles can exhibit a wide range of pulmonary function and severity of hepatobiliary disease. Consequently, the consensus committee strongly recommends that caregivers avoid making prognostic predictions based on genotype information in any individual with CF. Ancillary tests may help establish a diagnosis of CF either by revealing a phenotype, such as PI, or by identifying an ion channel abnormality.
Information regarding pancreatic exocrine function is valuable for both diagnostic and treatment purposes. When performed correctly, hour stool collection is very useful for determining pancreatic function and evaluating response to enzyme therapy; however, this test is not used routinely, because of technical and logistical complexities.
Alternative screening tests measure the fecal concentration of endogenous pancreatic enzymes. Because fecal trypsin and chymotrypsin tests may be inaccurate due to intraluminal degradation and cross-reactivity with ingested enzymes, the highly specific monoclonal test for fecal elastase, which is resistant to degradation, is preferred. Because reference values for fecal elastase measured by the polyclonal antibody test have not been established, and because the antibody displays some cross-reactivity with ingested enzymes, this test is considered less reliable.
In patients with CF who are at least 7 to 8 years old, serum trypsinogen values also may be used to assess pancreatic function. Additional ancillary tests are currently in use by clinicians to clarify the diagnostic status of individuals with less CF-specific gastrointestinal or pulmonary symptomatology. The nasal potential difference NPD test, which has been used in CF research for decades, has recently been introduced to clinical practice to aid diagnosis; 74 it may be particularly helpful in individuals with inconclusive sweat chloride values.
An NPD test showing a significant response to zero-chloride perfusate containing isoproterenol may be useful in ruling out a diagnosis of CF. Nevertheless, to date only 12 US centers have been validated by the Cystic Fibrosis Foundation for reproducible, accurate NPD testing using standardized procedures, and only 1 center has sufficient expertise with infant NPD to make this test a useful adjunct to NBS.
Because there are no clear reference values, validation studies, or standardized technical protocols for NPD testing for diagnostic purposes, the test should be used only to provide contributory evidence in a diagnostic evaluation. Intestinal ion channel measurements, such as Ussing chamber measurements of CFTR function from rectal biopsies, have no clearly established reference values and should be used for research purposes only at present. Individuals with suspected CF are identified for diagnostic evaluation from different pathways, including prenatal screening or NBS.
Diagnosis then may be made through various approaches, depending on age, genotype, and phenotype. Until the advent of widespread NBS for CF, suspicion for CF arose only from the appearance of symptoms or a family history of the disease. The primary test for confirming the diagnosis of CF is the sweat chloride test , performed according to the guidelines described earlier. This section presents diagnostic process recommendations for newborns with positive CF NBS, followed by recommendations for individuals presenting through other means.
These patients are likely to experience life-threatening CF lung disease at varying ages.