INTRODUCTION:

What is cystic fibrosis (CF): A genetic disorder affecting a protein in the body, CF is a hereditary ailment. A malfunctioning protein in the body damages the tissues, glands that produce sweat and mucus, and cells in people with cystic fibrosis. Normal mucus is slippery and protects the airways, digestive tract, and other organs and tissues. Cystic fibrosis causes mucus to become thick and sticky. As mucus builds up, it can cause blockages, damage, or infections in affected organs.

Children with cystic fibrosis were known to die. Thanks to medical advancements in lung transplants, medications, nutrition, and newborn screening, survival rates have increased. There are currently over 100,000 people living with cystic fibrosis globally, and about 40,000 children and adults in the United States. Cystic fibrosis children born between 2018 and 2022 should expect to live an average of 56 years. Cystic fibrosis babies born in 2021 are predicted to live to be 65 years of age or older, on average.

While some cystic fibrosis patients experience severe symptoms or potentially fatal complications, others have little or no symptoms at all. As a result of severe lung infections, pulmonary consequences, such as recurrent respiratory or pulmonary exacerbations, are the most prevalent and dangerous side effects of cystic fibrosis.

Treatments to enhance lung function and avoid or manage problems will be suggested by your healthcare practitioner. Receiving treatment can lengthen your life and enhance your quality of life. A genetic (inherited) disorder of the body's mucus glands, cystic fibrosis (CF) is a chronic, progressive, and often fatal condition. In children and young adults, cystic fibrosis (CF) predominantly affects the digestive and respiratory systems. Usually engaged as well are the reproductive system and sweat glands. The typical lifespan of a person with cystic fibrosis is about thirty years. Over 200 years have passed since the discovery of CF-like disease. In 1938, the illness was initially referred to as cystic fibrosis of the pancreas.¹

How Common Is CF?

The Cystic Fibrosis Foundation has gathered statistics indicating that around 30,000 Americans, 3,000 Canadians, and 20,000 Europeans suffer from cystic fibrosis. Though it affects all races and ethnic groups, white people whose origins are from northern Europe are the most likely to contract the disease. As a result, Asian Americans, Native Americans, and African Americans have lower rates of it. Every year, over 2,500 newborns in the US are diagnosed with CF. Additionally, one in every twenty Americans carries an aberrant "CF gene" but is unaffected by it. Most of these 12 million individuals are not aware that they are carriers^.1

Cystic Fibrosis and 20th century:

There is still debate about who should be credited with the first description of cystic fibrosis in the modern era. Although DA Christie and EM Tansey², along with Blackfan and Wolbach in 1933³, are often mentioned as pioneers in describing cystic fibrosis in the early 20th century, the connection between the disease and pancreatic conditions as well as bronchiectasis was not clearly understood at that time. These conditions were often attributed to Vitamin A deficiency.

It wasn't until 1936 that Professor Guido Fanconi made a significant breakthrough. In his paper titled “Das Coeliacsyndrombei Angeborenerzysticher Pankreasfibromatose und bronchiektasen,” Fanconi established a link between celiac disease and cystic fibrosis, including its effects on the pancreas and the lungs. His work, “Familiar Pancreatic Cystic Fibromatosis with Bronchiectasis,” played a crucial role in defining the relationship between these conditions and advancing the understanding of cystic fibrosis⁴. G. Fanconi (1892, Poschiavo, Suiza-1979, Zurich) developed his career as a paediatrician in the Children’s Hospital in Zurich; in 1934 the first case of cystic fibrosis of the pancreas was described, at least retrospectively, in a thesis written under his direction and almost a decade beforehand, in 1928, he published his observations concerning “celiac syndrome” in a group of children with digestive symptoms starting from breastfeeding and associative respiratory illness⁵.

The first descriptive correlation between the practice and histopathology of cystic fibrosis as an independent entity was carried out by Dorothy Andersen, (Dorothy Hansine Andersen 1901, Asheville, North Carolina – 1963, New York) a pathologist at Columbia Presbyterian Medical Center in New York and professor. In 1938, she communicated in May (American Pediatric Society) and published in August a detailed review of the signs of the disease, including its association with meconium ileus calling it “cystic fibrosis of the pancreas” “he diagnosis of cystic fibrosis of the pancreas can be made with certainty only by examining the duodenal contents for pancreatic enzymes or by microscopic examination of the pancreas.⁶

By 1944, it was becoming clear to a few interested doctors that cystic fibrosis didn't only impact the pancreas but also affected other organs like the lungs⁷This new understanding suggested that the name "cystic fibrosis" might not fully capture the nature of the disease. Sidney Farber, a Harvard Medical School professor, introduced the term "mucoviscidosis" based on his observations of patients who had died from the disease. He noted that it was a systemic illness affecting multiple organs, not just one.^8,9,10

The discovery of the CFTR gene has led to new research opportunities, such as using genetically modified rats in studies from 1992¹¹ to 1995. Researchers have also been investigating mutations and the function of the CFTR protein in cells. While many mouse models for cystic fibrosis (CF) show intestinal issues, they don’t typically have respiratory problems. However, there are two specific rat strains that do experience respiratory issues. In 1997, G. Kent et, al. described the phenotype of a congenic strain of “knock-out” rats, a congenic strain of back-crossing that developed early pulmonary illnesses spontaneously and progressively characteristic of fibrosis, inflammation and problems with the mucociliary clearance.^12,13,14.

More recently, one rat has been developed that specifically overexpresses the sodium ENaC canal in the respiratory epithelium to demonstrate that the transport of sodium per se may cause pulmonary illness similar to that of cystic fibrosis^15,16 The increase in the absorption of sodium in these rats led to an increase in the concentration of mucus, which caused a severe and spontaneous pulmonary illness comparable to CF, with inflammation through neutrophils, obstruction of mucus and little bacterial elimination which makes these rats a better model for the study of pulmonary issues of CF.^17,18,19

What are the symptoms of adult-onset cystic fibrosis?

Common symptoms of adult-onset CF include:

· Persistent Cough

· Shortness Of Breath

· Frequent Respiratory Infections

· Salty tasting skin

· Skin Rashes

· Skin Infections

· Difficulty Gaining Weight

· Bloating

· Diarrhoea

· Constipation²⁰

Cystic Fibrosis and Pregnancy:

If you have cystic fibrosis, you can still get pregnant and carry a baby to full term. However, you will need close monitoring throughout your pregnancy to keep both you and your baby healthy. To give yourself the best chance for a successful pregnancy, it's a good idea to consult with a high-risk obstetrician before you start trying to conceive.

· Evaluate your health.

· Determine whether it’s safe for you to get pregnant.

· Guide you through pregnancy.

You’ll also work closely with the pulmonologist who treats your cystic fibrosis throughout your pregnancy^21,22.

Effects on pregnancy:

During pregnancy, cystic fibrosis symptoms can become more noticeable. As the baby grows, it can put extra pressure on your lungs, making it harder to breathe. Additionally, constipation can be a common issue for women with cystic fibrosis²³

Other cystic fibrosis pregnancy complications include:

Premature Delivery: This happens when your baby is born before 37 weeks of pregnancy. Babies born too early might have trouble breathing or get infections.

Gestational Diabetes: This means high blood sugar during pregnancy. It can harm both the mother and baby, affecting organs like the kidneys and eyes, and might lead to problems with the baby’s development.

High Blood Pressure (Hypertension): This is when the blood pressure is too high. It can make it harder for blood to flow to the baby, which might slow the baby’s growth and increase the risk of early delivery.

Nutritional Deficiency: This occurs when you’re not getting the right nutrients, which can affect the baby’s growth in the womb^24,25,26

What are the symptoms of cystic fibrosis in babies?

· Frequent coughing

· Wheezing or shortness of breath

· Lung and sinus infections

Some individuals with mild cystic fibrosis may not show symptoms Trusted Source until closer to adulthood.²⁷

What causes symptoms of cystic fibrosis in babies?

Cystic fibrosis is a genetic disorder that a baby inherits from both parents. To have cystic fibrosis, a child must get a faulty gene from each parent. This condition affects the way the body handles chloride ions and water, leading to thick, sticky mucus building up in the lungs, pancreas, and other organs. The severity of the disease can vary from person to person, which might be due to additional genetic factors or environmental influences.^28,29,30

Cystic Fibrosis–Related Diabetes:

Cystic fibrosis–related diabetes affects approximately 50% of CF adults over the age of 30 and results in a significantly worsened prognosis and 6-fold higher mortality rate in comparison with CF patients without diabetes³¹. Cystic fibrosis–related diabetes is associated with lower lung function³²caused in part by increased colonisation of the lungs by bacteria such as Psuedomonas aeruginosa, S aureus, and Stenotrophomonasmaltophilia³³.

This leads to more lactate being produced, and things get worse when Pseudomonas aeruginosa, a type of bacteria, infects the area. Pseudomonas aeruginosa actually prefers using lactate for growth rather than other food sources. So, in someone with cystic fibrosis-related diabetes (CFRD), the conditions in the airway are more likely to support the growth of this bacteria.³⁴

Reproductive System Diseases:

Despite the fact that spermatogenesis is unaffected, problems in sperm transport render over 95% of men with CF infertile. Interestingly, two CFTR mutations are present in about half of all men who have normal lung function but congenital bilateral lack of the vas deferens³⁵. Meanwhile, because of exceptionally tenacious cervical mucus production and malnourishment, females with CF are less fertile than women in general. However, women with cystic fibrosis (CF) have the potential to become pregnant; those who do should receive appropriate counselling regarding contraception and childbearing choices³⁶. In fact, potential parents with cystic fibrosis must get thorough genetic counselling.

Digestive System Diseases:

About two-thirds of patients with cystic fibrosis (CF) have exocrine pancreas insufficiency from birth, and another 20% to 25% will acquire it throughout the first few years of life. By the time they are a year old, the majority will show indications of fat malabsorption³⁷. A lot of people with seemingly normal or marginal pancreatic function at birth eventually show overt signs of pancreatic insufficiency in adolescence or adulthood due to the progressive nature of CF-associated pancreatic illness. All all, over 85% of CF patients eventually experience clinically severe pancreatic insufficiency³⁸.

With regard to other CF‐associated digestive system disorders, 10% to 20% of newborns with CF present with meconium ileus characterized by obstruction of the bowel by meconium, which is a risk factor for poor CF prognosis³⁹ Rectal prolapse, which previously was rarely detected in children with CF, has been detected frequently in recent years and appears to be associated with constipation and/or malnutrition.

Treatment for cystic fibrosis includes

1. Medicines to clear the airway.

2. Improving the function of the faulty CFTR protein.

3. Breathing support, nutritional support, or surgery may be needed.

4. Airway clearance therapy (ACT).

5. Mucus thinning medication.

6. Pancreatic enzyme replacement therapies to help absorb food and nutrients.

7. Antibiotics to treat bacteria in the mucus.

Cystic fibrosis cannot be cured, but treatment can lessen symptoms, cut down on complications, and enhance quality of life. It is advised to closely monitor the condition and to take swift action when necessary to stop the advancement of CF, as this can extend life.

The goals of treatment include:

· Eliminating and dislodging pulmonary mucus

· Treating and avoiding intestinal blockage;

· Preventing and controlling lung infections

· Making sure you're getting enough food^41,42,43

Medications:

Options include:

· Antibiotics to treat and prevent lung infections

· Anti-inflammatory medications to lessen swelling in your lungs' airways

· Medication that targets gene mutations, including a new medication that combines three drugs to treat the most common genetic mutation causing CF and is considered a major achievement in treatment

· Medication to thin mucus, like hypertonic saline, to aid with coughing and enhance lung function Acid-reducing medications to help pancreatic enzymes work better⁴⁴

Specific drugs for diabetes or liver disease, when appropriate.

Medicationsthat target Genes:

For people with cystic fibrosis who have specific gene mutations, doctors might suggest using CFTR modulators. These newer medicines are designed to help the faulty CFTR protein work better. By doing this, they can improve lung function, help with weight gain, and reduce the amount of salt in sweat. CFTR modulators make a difference by fixing how the CFTR protein functions, which can help prevent lung problems and other issues. However, not all CFTR modulators work for everyone with cystic fibrosis, so the best choice depends on the specific mutation in the CFTR gene.

The FDA has approved these medications for treating CF in people with one or more mutations in the CFTR gene:

● The newest combination medication containing elexacaftor, ivacaftor and tezacaftor (Trikafta) is approved for people age 12 years and older and considered a breakthrough by many experts.

● The combination medication containing tezacaftor and ivacaftor (Symdeko) is approved for people age 6 years and older.

● The combination medication containing lumacaftor and ivacaftor (Orkambi) is approved for people who are age 2 years and older^.45

Airway Clearance Techniques:

Airway clearance techniques, also known as chest physical therapy (CPT), help clear mucus from the lungs and reduce infections and inflammation. These methods make it easier to cough up thick mucus by loosening it. The techniques can involve special breathing and coughing methods, devices that you use with your mouth, therapy vests that use vibrations to break up mucus, and physical therapy for the chest. Overall, these techniques help clear mucus from the lungs, leading to better breathing and fewer infections.

· One common method is clapping with cupped hands on the front and back of the chest.

· Other techniques include special breathing and coughing exercises to help loosen the mucus.

Your doctor will instruct you on the type and frequency of chest physical therapy that's best for you^46,47.

Pulmonary Rehabilitation:

Your doctor might suggest a long-term program to enhance your lung function and overall health. Pulmonary rehabilitation is often done on an outpatient basis and may include various treatments and exercises tailored to improve your respiratory health.

· Physical exercise that may improve your condition

· Breathing techniques that may help loosen mucus and improve breathing

· Nutritional counselling^48,49.

Surgical and other Procedures:

Surgery:

A lung transplant can be beneficial for individuals with severe lung disease and respiratory failure. Advanced liver conditions like cirrhosis, a liver transplant might be considered.⁵⁰

Options for certain conditions caused by cystic fibrosis include:

· Nasal and sinus surgery: Your doctor might suggest surgery to remove nasal polyps that block breathing or to treat chronic sinus infections.

· Oxygen therapy: If your blood oxygen levels are low, your doctor may recommend breathing pure oxygen to help prevent high blood pressure in the lungs.

· Non-invasive ventilation: Often used during sleep, this method involves wearing a mask over your nose or mouth to provide extra air pressure. It helps improve breathing and may be used with oxygen therapy to enhance lung function and aid in clearing mucus^.[51].

· Feeding tube: Since cystic fibrosis can affect digestion, your doctor might recommend a feeding tube to ensure you get enough nutrition. This tube could be temporarily placed through your nose into your stomach or permanently implanted in your abdomen. It helps provide extra calories without interfering with eating normally.

· Bowel surgery: If a blockage occurs in your bowel, you might need surgery to remove it. Surgery may also be required if a part of your intestine slides into another section (intussusception).

· Lung transplant: For severe breathing issues, serious lung problems, or if antibiotics are no longer effective, a lung transplant might be considered. Since diseases like cystic fibrosis can cause long-term damage and bacterial buildup in the airways, both lungs usually need to be replaced.

Cystic fibrosis itself does not come back in transplanted lungs. However, other CF-related issues like sinus infections, diabetes, problems with the pancreas, and osteoporosis can still happen after a lung transplant.

· Liver transplant: For severe cystic fibrosis-related liver disease, such as cirrhosis, liver transplant may be an option. In some people, a liver transplant may be combined with lung or pancreas transplants ^[52].

REFERENCE:

1. National Heart, lung, and blood institiye An official website of the United States Government

2. Christie DA, Tansey EM (2004) Cystic Fibrosis. In: Christie DA, Tansey EM (eds) (2004) Wellcome Witnesses to Twentieth Century Medicine. Volume 20. London: The Wellcome Trust Centre for the History of Medicine at UCL, this volume. ISBN 0 85484 086 9.

3. Blackfan KD, Wolbach SB. Vitamin A deficiency in infants. Journal of Paediatrics. 1933; 3: 679-706.

4. Fanconi G, Uehlinger E, Knaver C. Das Coeliac syndrome bei Angeborenerzysticherpankre as fibromatose und bronchiektasen. Wien Medizinische Wochenschrift. 1936; 86: 753-756.

5. Fanconi G. Der intestinaleinfantilismus und ähnlicheformen der chronischenVerdauungsstörung. Bibliotheca Paediatrica. 1928; 21. Link: https://goo.gl/iFvYhQ

6. Andersen DH. Cystic fibrosis of the pancreas and its relation to celiac disease. A clinical and pathologic study. American Journal of Diseases of Children. 1938; 56: 344-399. Link: https://goo.gl/85yC15

7. Andersen DH. The present diagnosis and treatment of cystic fibrosis. Proc Roy Soc Med. 1949; 42: 25-31.

8. Farber S. Pancreatic insufficiency and the celiac syndrome. 1943; 229: 653-682. Link: https://goo.gl/tcHi8t

9. Fleming A. On the Antibacterial Action of Cultures of a Penicillium, with Special Reference to their Use in the Isolation of B. influenzæ. British Journal of Experimental Pathology. 1929; 10: 226-236. Link: https://goo.gl/zZh3c9

10. Andersen DH, Hodges RC. Celiac syndrome. Genetics of cystic fibrosis of the pancreas with consideration of the etiology. Am J Dis Child. 1946; 72: 62-80. Link: https://goo.gl/FkLXcJ

11. Bodian M. Fibrocystic Disease of the Pancreas: A Congenital Disorder of Mucus Production-Mucosis. Heinemann, London. 1952 Link: https://goo.gl/rg2B8b

12. Di Sant’Agnese PA, Andersen DH. Celiac syndrome. Chemotherapy in infections of the respiratory tract associated with cystic fibrosis of the pancreas; observations with penicillin and drugs of the sulphonamide groups, with special reference to penicillin aerosol. American Journal of Diseases of Children. 1946; 72: 17-61. Link: https://goo.gl/xusQPy

13. Darling RC, Di Sant’Agnese PA, Perera GA, Andersen DH. Electrolyte abnormalities of sweat in fibrocystic disease of pancreas. American Journal of Medical Science. 1953; 225: 67-70. Link: https://goo.gl/YreU7i

14. Di Sant’Agnese PA, Darling RC, Perera GA, Shea E. Abnormal electrolyte composition of sweat in cystic fibrosis of the pancreas: Clinical significance and relationship to the disease. Pediatrics. 1953; 12: 549-563. Link: https://goo.gl/PyygMt

15. Gibson LE, Cooke RE. A test for concentration of electrolytes in sweat in cystic fibrosis of the pancreas utilizing pilocarpine iontophoresis. Pediatrics. 1953; 23: 545-549.

16. Shwachman H, Kulczycki LL (1958) Long term study of one hundred five patients with cystic fibrosis. Am J Dis Child. 96: 6-15. Link: https://goo.gl/D7K1GL

17. Stollar F, VillacAdde F, Cunha MT, Leone C, Rodrigues JC (2011) Shwachman-Kulczycki score still useful to monitor cystic fibrosis severity. Clinics. 66: 979–983. Link: https://goo.gl/dBXGLc

18. Bishop HC, Koop CE (1957) Management of meconium ileus, resection, Roux-en-Y anastomosis and ileostomy irrigation with pancreatic enzymes. Ann Surg. 145: 410-414. Link: https://goo.gl/zUJfsz

19. Noblett HR (1969) Treatment of uncomplicated meconium ileus by gastrografin enema. A preliminary report. J PediatrSurg. 4: 190-197. Link: https://goo.gl/pH2Dsc

20. Steinberg AG, Shwachman H, Allen FH, Dooley RR. Linkage Studies with Cystic Fibrosis of the Pancreas. Am J Hum Genet. 1956; 8: 162-166. Link: https://goo.gl/4yYQPC

21. Conneally PM, Merritt AD, Yu PL Tex Rep Biol Med. 1973; 31: 639-650.

22. Knowles M, Gaztzy J, Boucher R. Increased bioelectric potential difference across respiratory epithelia in cystic fibrosis. NEngl J Med. 1981; 305: 1489-1495. Link: https://goo.gl/oS7LsS

23. Quinton PM. Chloride impermeability in cystic fibrosis. Nature. 1983; 301: 421-422. Link: https://goo.gl/bYHcUY

24. Quinton PM, Bijman J. Higher bioelectric potentials due to decreased chloride absorption in the sweat glands of patients with cystic fibrosis. N Engl J Med. 1983; 308: 1185-1189. Link: https://goo.gl/LnD9By

25. Tsui LC, Buchwald M, Barker D, Braman JC, Knowlton R, et al. Cystic fibrosis locus defined by a genetically linked polymorphic DNA marker. Science. 1985; 230: 1054-1057. Link: https://goo.gl/NwA6Ky

26. Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, et al. (1989) Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA.Science 245: 1066-1073. Link: https://goo.gl/Nd7cWd

27. Rommens JM, Iannuzzi MC, Kerem B, Drumm ML, Melmer G, et al. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. 1989; 245: 1059-1065. Link: https://goo.gl/ktY8pj

28. Kerem B, Rommens JM, Buchanan JA, Markiewicz D, Cox TK, et al. Identification of the cystic fibrosis gene: genetic analysis. Science. 1989; 245: 1073-1080. Link: https://goo.gl/hmMmHM

29. Anderson MP, Gregory RJ, Thompson S, Souza DW, Paul S, et al. Demonstration that CFTR is a chloride channel by alteration of its anion selectivity. Science. 1991; 253: 202-205. Link: https://goo.gl/jbcY7y

30. Anderson MP, Berger HA, Rich DP, Gregory RJ, Smith AE, et al. Nucleoside triphosphates are required to open the CFTR chloride channel. Cell. 1991; 67: 775-784. Link: https://goo.gl/PhRMfb

31. Scholte BJ, Davidson DJ, Wilke M, De Jonge HR. Animal modelsofcysticfibrosis. JournalofCystic Fibrosis. 2004; 3: 183-190. Link: https://goo.gl/VaYBHM

32. Snouwaert JN, Brigman KK, Latour AM. An animal model for cystic fibrosis made by gene targeting. Science. 1992; 257: 1083. Link: https://goo.gl/qaWfhc

33. Clarke LL, Grubb BR, Gabriel SE. Defective epithelial chloride transport in a gene targeted mouse model of cystic fibrosis Science. 1992; 257: 1125-1128. Link: https://goo.gl/nv4NRJ

34. Dorin JR, Dickinson P, Alton EW. Cystic fibrosis in the mouse by targeted insertional mutagenesis. Nature.1992; 359: 211-215. Link: https://goo.gl/Tr7Vy7

35. Ratcliff R, Evans MI, Cuthbert AW. Production of a severe cystic fibrosis mutation in mice by gene targeting. Nat. Genet. 1993; 4: 35-41. Link: https://goo.gl/FHBJ19

36. Kent G, Iles R, Bear CE. lung disease in mice with cysticfibrosis. J Clin Invest. 1997; 100: 3060-3069. Link: https://goo.gl/RQu3jp

37. Mall M. Overexpression of ENaC in mouse aiways: a novel animal modelforchronicbronchitis and cystic fibrosis lungdisease. PediatrPulmonol. 2003; 121: 137.

38. Medically reviewed by Adithya Cattamanchi. Pulmonology — Written by Stephanie Watson on August 7, 2019

39. Medically reviewed by Mia Armstrong— Written by Catherine Crider on September 14, 2023

40. Brennan AL, Geddes DM, Gyi KM, Baker EH. Clinical importance of cystic fibrosis-related diabetes. J Cyst Fibros. 2004; 3:209–222.

41. Milla CE, Warwick WJ, Moran A. Trends in pulmonary function in patients with cystic fibrosis correlate with the degree of glucose intolerance at baseline. Am J Respir Crit Care Med. 2000; 162: 891–895.

42. Limoli D, Yang J, Khansaheb M, et al. Staphylococcus aureus and pseudomonas aeruginosa co-infection is associated with cystic fibrosis-related diabetes and poor clinical outcomes. Eur J ClinMicrobiol Infect Dis. 2016; 35: 947–953.

43. Van Sambeek L, Cowley ES, Newman DK, Kato R. Sputum glucose and glycemic control in cystic fibrosis-related diabetes: a cross-sectional study. PLoS ONE. 2015; 10: e0119938.

44. Garnett JP, Kalsi KK, Sobotta M, et al. Hyperglycaemia and pseudomonas aeruginosa acidify cystic fibrosis airway surface liquid by elevating epithelial monocarboxylate transporter 2 dependent lactate-H+ secretion. Sci Rep. 2016; 6:37955.

45. Moran A, Becker D, Casella SJ, et al. Epidemiology, pathophysiology and prognostic implications of cystic fibrosis-related diabetes. Diabetes Care. 2010; 33: 2677–2683.

46. Cystic Fibrosis Trust. Management of Cystic Fibrosis Related Diabetes Mellitus. London: Cystic Fibrosis Trust; 2004.

47. Chillón M, Casals T, Mercier B, et al. Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. N Engl J Med. 1995; 332(22): 1475‐1480.

48. Sueblinvong V, Whittaker LA. Fertility and pregnancy: common concerns of the aging cystic fibrosis population. Clin Chest Med. 2007;28(2):433‐443.

49. Bronstein MN, Sokol RJ, Abman SH, et al. Pancreatic insufficiency, growth, and nutrition in infants identified by newborn screening as having cystic fibrosis. J Pediatr. 1992; 120(4 Pt 1): 533‐540.

50. Ledder O, Haller W, Couper RT, Lewindon P, Oliver M, et al. Cystic fibrosis: an update for clinicians. Part 2: hepatobiliary and pancreatic manifestations. J GastroenterolHepatol. 2014; 29(12): 1954‐1962.

51. Tan S, Coffey MJ, Ooi CY. Differences in clinical outcomes of paediatric cystic fibrosis patients with and without meconium ileus. J Cyst Fibros. 2019; 18(6): 857‐862.

52. Mayo Clinic in Rochester, Minnesota, Mayo Clinic in Phoenix/ Scottsdale, Arizona, and Mayo Clinic in Jacksonville, Florida, have been recognized among the top Pulmonology hospitals in the nation for 2024-2025 by U.S. News & World Report.

Received on 17.02.2025 Revised on 15.03.2025

Accepted on 03.04.2025 Published on 10.07.2025

Available online from July 17, 2025

Asian J. Pharm. Res. 2025; 15(3):347-352.

DOI: 10.52711/2231-5691.2025.00054

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.