Constipation and DIOS: Diagnosis, differential diagnosis, and management
Abstract
Cystic Fibrosis (CF) is a complex disorder that requires multidisciplinary expertise for effective management. The GALAXY study estimated the prevalence of constipation to be about 25% among People with Cystic Fibrosis (PwCF), identifying it as one of the common gastrointestinal (GI) symptoms within this patient population. Quality of Life (QoL) assessments uncovered high patient dissatisfaction, highlighting the imperative need for enhanced treatment strategies. Similarly, Distal Intestinal Obstruction Syndrome (DIOS) is a unique condition exclusive to PwCF that, if left undiagnosed, can lead to considerable morbidity and mortality. Given the broad spectrum of differential diagnoses for abdominal pain, including constipation and DIOS, it is paramount for healthcare providers to possess a clear understanding of these conditions. This paper aims to delineate various differentials for abdominal pain while elucidating the pathogenesis, diagnostic criteria, and treatment options for managing constipation and DIOS in PwCF.
1 INTRODUCTION
Cystic fibrosis (CF) is a chronic, multisystemic autosomal recessive genetic disorder associated with many comorbidities that can adversely impact individuals' quality of life (QOL). Some of the most common manifestations of CF occur in the gastrointestinal (GI) tract, namely constipation and distal intestinal obstruction syndrome (DIOS).
Constipation is a very common GI symptom in People with Cystic Fibrosis (PwCF) with a wide prevalence of 10%–57%.1 The Longitudinal Multicenter Study to Determine the Patient-reported Prevalence of GI Symptoms in Persons with CF (GALAXY) noted the prevalence of constipation to be 25%.2, 3 GALAXY Observational Study electronic Patient-Reported Outcome Measures (ePROMs) accurately reflect GI manifestations in PwCF.3 The three symptom-based questionnaires included in the validated GI ePROMS were: Patient Assessment of Gastrointestinal Symptoms (PAGI-SYM), Patient Assessment of Constipation Symptoms (PAC-SYM), and Patient Assessment of Constipation Quality of Life (PAC-QOL). The goal of the GALAXY study was to assess the period prevalence of multiple GI symptoms in PwCF and their impact on their quality of life whether on or off various GI medications. Additionally, non-GI providers comfort with treating GI symptoms was evaluated and although 80%–90% of providers expressed comfort in managing constipation, patient dissatisfaction with their existing treatments was high as reported by PAC-QOL.3 Therefore, it is relevant to any CF provider, not just gastroenterologists, to be familiar with the latest diagnostic and therapeutic guidelines on constipation and relevant nuances in PwCF to provide proper care.
Another common GI condition seen in PwCF is Distal Intestinal Obstruction Syndrome (DIOS). This syndrome was first described by a surgeon in 1945 when infants with CF presented with inspissated meconium causing distal intestinal obstruction in neonatal patients.4 At this time, it was denoted meconium ileus equivalent (MIE). Over time the definition was expanded to include a variety of clinical conditions because of incomplete and complete bowel obstruction, leading to the establishment of distal intestinal obstructive syndrome (DIOS).5 However, there was ambiguity with the use of this term as within it clinicians included other diagnoses such as intussusception, palpable intestinal masses, rectal prolapse, and constipation. While all these conditions were common comorbidities of CF, they have different pathophysiology, risk factors, diagnosis, and treatment. Thus, in 2010 the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) convened and conducted a study to differentiate between DIOS, MIE and constipation.5 This distinction subsequently led to more accurate diagnoses, better treatment, and a more complete understanding of the intersection between CF and different manifestations of abdominal pain. This review will discuss updates on the pathophysiology, differential diagnosis, and management of constipation and DIOS in PwCF.
2 CONSTIPATION
2.1 Definition and pathophysiology
The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) CF Working Group defines constipation as abdominal pain and/or distention, either increased stool consistency or decreased frequency of bowel movements in the last few weeks or months, and the improvement of those symptoms when treated with laxatives.5 Since PwCF experience chronic constipation, they may still have bowel movements daily and still be constipated, it is important to consider the stool consistency and frequency per the ESPGHAN guidelines to accurately diagnose patients.6 The GI manifestations of CF are due to the CFTR gene mutation that alters chloride, bicarbonate and fluid equilibrium. Due to this mutation, chloride cannot be transported out of cells and bicarbonate, which is essential to neutralize gastric acid to aid in digestion, is decreased due to the impaired pancreas. The pancreas impairment also causes less fluid emptied into the intestines.7-9 Acidified mucous layer along with dehydrated intestinal fluid leads to delayed intestinal transit attributing to constipation in these patients.
2.2 Diagnosing constipation in PwCF
Constipation in PwCF is a clinical diagnosis based on history and physical exam. Certain differential diagnoses (discussed later in this review) should be considered specifically in the CF population which presents with symptoms mimicking constipation.
Clinical symptoms for constipation in PwCF include straining, fullness, incomplete bowel movements, distension, and abdominal pain.7 Detailed history including onset and duration of symptoms, frequency, consistency of stools using the Bristol stool form scale, diet, and use of maneuvers or medicine to assist in defecation should be obtained.10 It is useful to assess information regarding pancreatic function, weight fluctuations, surgical history, and adherence to PERT.11 Physical examination should include digital rectal exam, inspection of the perineum and lumbosacral region to look for structural abnormality such as imperforate anus, spinal cord abnormality like spina bifid, and meningomyelocele.10 If a detailed history or physical examination exposes any red flag symptoms such as bilious vomiting, bloody stools, or fever, further testing must be elicited considering other differential diagnoses.11 Generally, history and clinical assessment is enough to diagnose constipation and further radiographic imaging and testing should not be necessary in most patients. As such, empirical treatment can be started.6
2.3 Differential diagnosis
2.3.1 Constipation versus DIOS
One of the main differential diagnoses specific for PwCF while evaluating for acute onset constipation is DIOS. Although DIOS and constipation can present concurrently and have similar symptoms, they are distinctly different and require different management. The pathophysiology, diagnosis and management of DIOS follows in the next section of this article. Typically, DIOS presents with acute onset symptoms compared to constipation.12 If the diagnosis is not evident, abdominal radiographs or CT with oral contrast should be obtained.12 Imaging can distinguish DIOS from constipation because DIOS presents with stool obstruction in the distal small bowel or proximal right colon as opposed to the diffuse presence of stools in the entire colon, indicating constipation.6, 12
2.3.2 Constipation versus IBS with constipation
Irritable bowel syndrome (IBS) is a disorder of the gut–brain axis interaction (DGBI) that has a significant impact on people's QOL.13 According to the Rome IV diagnostic criteria, IBS is a symptom-based criteria diagnosed based on abdominal pain present for at least 1 day/week for the past 3 months associated with at least 2 of the following: defection, change in frequency of stool, and/or change in form of stool with symptom onset for 6 months at least.14 One subtype of IBS is IBS with predominant constipation (IBS-C).14 IBS-C causes one-third of all IBS cases.13 It may be challenging to differentiate IBS-C from those with constipation due to overlapping symptoms.
2.3.3 Overlap of SIBO and constipation
Proposed mechanisms for SIBO in CF include thickened mucus, and poor intestinal motility that causes stasis of secretion which serves as a nidus for bacterial accumulation. In addition, dysbiosis, pancreatic insufficiency, abdominal surgeries, and use of medications (such as opioids, acid suppressants, steroids, antibiotics) are other factors that contribute.15, 16 PwCF are at risk for Small Intestine Bacterial Overgrowth (SIBO), with a prevalence as high as 56% in PwCF.16 Previously SIBO was defined by the presence of more than 105 colony-forming units (CFU) of colonic bacteria per 1 ml of small intestinal fluid. Whether a bacterial count of >105 is needed to make a diagnosis of SIBO is a topic of debate.17 Recent literature suggests that bacterial counts >103 may be more sensitive for defining SIBO.18, 19 Common clinical manifestations of SIBO include bloating and distension with excess flatus, weight loss, abdominal pain, constipation and steatorrhea.8, 20 Since these symptoms are nonspecific and overlap with conditions such as constipation, IBS, malabsorption, its specific diagnosis may be challenging, and many believe it is a syndrome and not a disease.8 Duodenal fluid aspiration and culture is the gold standard for diagnosis of SIBO, although it is difficult to obtain samples and there is a lack of standardization for diagnostic bacteria values. Instead, breath tests measure exhaled hydrogen and methane gas, both indicating the presence of bacteria in the gut that metabolized ingested lactulose or glucose. These are an indirect method to diagnose SIBO, though they have lower sensitivity and specificity for diagnosis as well as poor standardization of cut-off values.21 New diagnostic approaches such as metagenomic sequencing to understand the bacterial genome and meta-transcriptomics to study the mRNA expressed in GI samples, are being explored in the general population to overcome the limitations of breath tests. One novel technology, the Atmo® Gas Capsule, uses a capsule that travels through the GI tract to determine localized gas concentrations affected by bacteria. This gas-sensing capsule could be a new way to directly determine microbial concentration in the gut.21 Due to a lack of standardized diagnostic testing, symptoms of weight loss along with bloating in PwCF can justify a trial of empiric antibiotics for SIBO.16 A commonly used antibiotic used for SIBO treatment is the non-systemically absorbed antibiotic rifaximin which has been shown to be effective,16 but not FDA approved for SIBO treatment. In fact, SIBO has no FDA-approved medications.
2.3.4 Functional constipation versus dyssynergic defecation/motility disorders
Dyssynergic defecation is the uncoordinated contraction of anorectal and abdominal muscles leading to stool retention and fecal incontinence.10 In children with CF, this condition is not well-prescribed although rectal prolapse which is often seen in patients with dyssynergia is a common presentation of CF in children. However, there are limited studies that describe fecal and urinary incontinence in CF caused by increased pressure on the pelvic floor muscle due to frequent coughing, diarrhea, malabsorption, and dysbiosis.22, 23 Anorectal manometry (ARM) is a physiologic test used to diagnose dyssynergic defecation by measuring sphincter tone, rectoanal inhibitory reflex, and pressure changes during defecation.10 In patients with normal ARM and refractory constipation despite adequate treatment, colonic manometry is an intervention to diagnose colonic motility disorders and assess need for surgical intervention such as cecostomy and anterograde continent enema, nerve stimulation and colonic resection. Algorithm 1 presents step-wise guidelines for refractory constipation needing further evaluation.
2.4 Management
There is no specific algorithm for the treatment of constipation in PwCF, however, all management should follow a gradual step-up therapy approach like the general population.12 It is suggested that a multidisciplinary team, including a GI provider, follows PwCF periodically to ensure compliance and improvement in QoL. Described below are recommended management methods and an algorithm (Algorithm 1) has been included to describe how gradual step-up therapy can be used.
2.4.1 Lifestyle modifications
Some nonmedical methods to reduce constipation in PwCF include hydration and exercise.12 Supplementation of either soluble or insoluble fiber is recommended for adults with constipation because it increases stool weight and softens stool through fiber mass, increased water retention, and increased presence of fermented bacteria.24 The recommended total daily fiber intake is 20–30 g/day with no benefit over 25–30 g/day.24 However, the benefit is unclear in PwCF because fiber may worsen constipation due to decreased transit and viscosity of stool in PwCF.12 Additionally, there is no definitive conclusion regarding probiotics in aiding constipation in children whether alone or in combination with other treatment options; one study provides limited evidence that a synbiotic preparation may cause treatment success over a placebo.25
2.4.2 Osmotic laxatives
Osmotic laxatives are commonly used as first-line treatment for constipation in PwCF.12 Osmotic laxatives pull in fluid from the body or retain fluid present, causing an increase of water in the large intestine that softens the stool.26 Polyethylene glycol (PEG) is the most commonly used; GALAXY study showed that 41.3% of participants were using constipation medications and PEG was the most commonly used (37.1%).7 However, if patients do not tolerate PEG, other osmotic laxatives including lactulose or magnesium citrate preparations can be tried.12
2.4.3 Stimulant laxatives
Stimulant laxatives are the second line of treatment for constipation in PwCF. Senna causes the bowel to empty by stimulating peristalsis and it is helpful when stool is already soft.26 Sodium picosulphate and bisacodyl are other stimulant laxatives that can be used. Chronic laxative use, particularly senna causes cell death and apoptosis with deposition of lipofuscin leading to dark pigmentation in the colon called melanosis coli. Melanosis coli will typically resolve with cessation of laxatives and is not associated with increased colon cancer risk.27
2.4.4 Lubiprostone
Lubiprostone is a Type 2 chloride channel activator that causes chloride secretion and leads to prostanoid receptor signaling to reduce the intestinal transit time.12 Studies have shown good safety profile for ≥6 years of age, though its efficacy is yet to be established in pediatrics.28 In a pilot study with seven PwCF, lubiprostone improved overall symptoms of constipation measured by PAC-SYM.29 Animal studies have demonstrated that lubiprostone increases luminal fluid and alkalinity in CF-nulled mice. Theoretically, this should help prevent DIOS and alleviate constipation.30
2.4.5 Linaclotide
Linaclotide is a guanylate cyclase-C ligand agonist that increases cGMP intracellularly and leads to increased intestinal fluid secretion by activating CFTR.12 Linaclotide is now FDA approved for adults and kids >6 years for functional constipation.31 Studies have shown that in CF mouse models, Linaclotide improves GI transit through inhibition of NHE3-mediated sodium absorption which increases luminal fluid.32 However, randomized control trials are needed to establish its efficacy in this patient population.
2.4.6 Plecanatide
Plecanatide is a 16-amino acid peptide that increases cGMP levels leading to activation of the guanylate cyclase C receptor on enterocytes. Similarly to Linaclotide, activation of CFTR increases fluid and electrolyte secretion, however, Plecanatide is a uroguanylin analog with two disulfide bonds. Plecanatide is FDA-approved to treat chronic idiopathic constipation and IBS-C.13 Significant improvement of IBS-C symptoms as well as increased spontaneous bowel movements have been observed by two RCTs in non-CF adults using Plecanatide.33 No data is available to establish the use of this medication in PwCF for the treatment of constipation.
2.4.7 Prucalopride
Prucalopride is a dihydrobenzofuran carboxamide 5-HT4 receptor agonist, thereby promotes ACh release, stimulates colonic smooth muscle contractions and peristalsis. It also activate GC-C receptors, leading to increased secretion of Cl- and HCO3-, followed by Na+ and water secretion. It is approved for adults with CIC and shown to improve spontaneous bowel movements and QOL related to constipation.10 There is no validated research data about its efficacy in the treatment of constipation in PwCF.
2.4.8 Tenapanor
Tenapanor uses a novel mechanism that inhibits the sodium/hydrogen exchanger isoform 3 (NH3) which absorbs sodium on the apical surface of the intestines, therefore Tenapanor decreases sodium and phosphate absorption while increasing water volume in the intestines. Though originally FDA-approved for adjuvant treatment of hyperphosphatemia in hemodialysis patients, Tenapanor has been approved for the treatment of IBS-C.13, 34 Though not FDA approved for PwCF in specific, there are animal studies that demonstrate oral administration of tenapanor to CFTR-nulled mice prevents intestinal obstruction and improves gastrointestinal transit time30, 35
2.4.9 Vibrating capsule
Vibrating capsule is a novel therapeutic modality in the treatment of chronic idiopathic constipation. The capsule is ingested orally, vibrates intraluminally, and stimulates bowel movements.36 In a double-blind, placebo-controlled trial vibrating capsule showed a significant increase of Complete Spontaneous Bowel Movements (CSBMs) for at least 6 of the weeks as well as improved straining and stool consistency when compared to the placebo group.36 Side effects were mild and a vibrating sensation was felt by 11% of participants. Though the current study excluded patients with organic disease including CF, more research is needed to explore its use to treat constipation in PwCF.36
3 DIOS
3.1 Definition and prevalence
The European Society for Pediatric Gastroenterology concluded that DIOS and MIE essentially refer to the same condition. MIE refers to an accumulation of inspissated meconium causing an obstruction in the distal and proximal colon in neonates, while DIOS refers to the same clinical presentation after the neonatal period.37 However, there is a clear difference between DIOS and constipation.37 DIOS is a more acute condition and presents with fecal matter in a more concentrated area of the colon, such as the distal small bowel and/or proximal right colon.38 DIOS can be separated into incomplete and complete manifestations. Complete DIOS has three criteria including: (1) a complete obstruction of the intestine, observed with symptoms of bilious vomiting or fluid levels seen on abdominal radiography, (2) a fecal mass in the ileo-cecum, and (3) abdominal pain/distention.5 Incomplete DIOS is similar to complete DIOS as it presents with a fecal mass in the ileo-cecum and abdominal pain/distention but lacks a sign of intestinal obstruction (absence of bilious emesis and radiological signs of obstruction).5
The consensus establishing clear definitions of DIOS led to more accurate evaluations of incidences of DIOS in children and adults. Previously, it was proposed that there is a similar incidence of DIOS in both pediatric and adult CF patients. However, a prospective longitudinal study conducted by Munck et al. which used the ESPGHAN definitions concluded that the incidence of DIOS is similar in pediatric patients and adult patients and occurs in 10%–15.8% of the CF population.39
3.2 Pathophysiology
CFTR is expressed weakly in the stomach, but well localized throughout the intestine.40 CFTR dysfunction leads to reduced chloride and water secretion into the intestinal lumen as well the gain of function in the epithelial sodium channel (ENaC), causing increased fluid reabsorption (Figure 1).12, 41 There is also evidence of enteric neuromuscular dysfunction and hypertrophy of the muscularis mucosa, leading to decreased motility and an increased risk of intestinal obstruction.12, 38 In addition to the secretory dysfunction leading to thickened intestinal content; impaired motility, reduced bile salt and fat malabsorption may be other factors that contribute to DIOS.42 Though there is conflicting data about the role of pancreatic insufficiency and fat malabsorption, as the incidence of DIOS did not change after treatment with pancreatic enzymes.5
Few risk factors have been identified to predispose an individual to DIOS. A European study concluded that almost half of the participants with DIOS presented with meconium ileus at birth.5, 43 Another study found that the probability of developing an episode of DIOS after a previous episode was 10 times higher compared to not having experienced a previous episode.5, 44 Dehydration and respiratory illness including CF exacerbation can precipitate DIOS.12, 38, 45 Lung transplantation serves as another risk factor for DIOS, with an incidence of 10%–20%. It has been noted that 10% of those developing DIOS following a lung transplant need laparotomy. Though exact etiology is unknown, postoperative ileus, prolonged bed rest, prior abdominal surgeries, dysmotility due to opioid medications may be factors for poor outcome.12, 46, 47
3.3 Differential diagnosis
Due to the multifaceted nature of DIOS, it is important to distinguish it from other conditions that present with overlapping symptoms (Table 1).
| Surgical conditions | Acute exacerbation of chronic diseases | Others |
|---|---|---|
Acute appendicitis |
Constipation with impaction |
Malignancy |
Appendicular abscess |
Crohn's disease |
Fibrosing colonopathy |
Volvulus |
||
Intussusception |
||
Adhesions leadings to obstruction |
DIOS presents with multiple air-fluid levels and fecal load specifically in the ileocecal region.48 CT findings in DIOS include colonic wall thickening, mural striation, inspissated soft tissue masses in the distal ileum, a decompressed cecum, and an increased amount of peri colonic fat, commonly in the right colon.12, 49
Constipation presents more gradually and fecal impaction is seen on abdominal radiograph in the whole colon, while DIOS presents acutely with concentrated fecal impaction primarily in the ileocecal area.5
Characteristic clinical features of DIOS may mimic acute appendicitis, which presents with right lower quadrant pain.50 Intussusception, especially that of the ileocecum, is another differential diagnosis to be considered, as it has been described in 1% of PwCF.12 The use of abdominal ultrasonography can help to distinguish intussusception and appendicitis from DIOS.38 A diagnosis of intussusception can be confirmed with the use of sonography showing “donut sign” on transverse imaging. Computed Tomography (CT) scan can be helpful to diagnose acute surgical conditions such as appendicular abscess, volvulus and acute appendicitis (especially when ultrasound is inconclusive).
Crohn's disease can present with obstructive symptoms in the ileocolonic region. However, the pathophysiology underlying this condition is different as the underlying mechanism is inflammation. Additionally, a diagnosis of IBD can be confirmed with colonoscopy and biopsy.51 IBD is an important differential to be considered as higher prevalence has been noted in this population.52, 53
Fibrosing colonopathy can present with similar symptoms of abdominal pain, distention, vomiting, and constipation and should also be included in the differential.38 This condition encompasses a different pathophysiology as it involves recurrent ischemia rather than chronic inflammation, due to inappropriately high doses of PERT.6 Endoscopically it shows areas of inflammation with erythema, edema and cobble stone appearance (Picture 1). There can be areas of ulcerating, bleeding and structuring.
There is an increased risk of gastrointestinal malignancies in PwCF, and symptoms of these cancers can mimic symptoms of DIOS. Adults with CF are 5–10 times at higher risk than the general population and 25–30 times at increased risk after organ transplantation. Hence guidelines recommend doing screening colonoscopy at 40 years of age and for those with organ transplant screening starts at 30 years of age or within 2 years of transplant.54
3.4 Management
A stepwise approach is implemented for treatment of DIOS. The treatment differs based on whether the patient has complete or incomplete DIOS. The below regimen is based on the algorithm recommended by Cystic Fibrosis Foundation (CFF).
3.4.1 Incomplete DIOS
If the patient presents without signs of obstruction (minimal pain, no vomiting), no prior GI surgery, they can be treated in an outpatient setting. Bowel clean out is the mainstay of treatment. PEG is the first line laxative that is used. Ideally, large doses of PEG is recommended. However, if a patient is unable to tolerate large volumes, then smaller doses at frequent intervals can be tried. Enemas are very helpful if able to be tolerated and supported at home. If this does not help, patients should be referred to the ED for inpatient treatment.
3.4.2 Complete DIOS
If patients are presenting with symptoms of obstruction, there is a high likelihood for complete DIOS. Imaging, such as a 2-view abdominal XR (AXR) and non-IV contrast CT of the abdomen and pelvis will help in diagnosing in DIOS and ruling out other diagnoses with similar symptoms (refer to Algorithm 2). If patients present with peritoneal signs, surgeons should be consulted due to risk of bowel perforation. Air fluid levels on imaging warrants treatment with NasoGastric (NG) tube decompression and Gastrograffin enema followed by the administration of a PEG solution after clinical improvement. Therapeutic response can consequently be confirmed with a repeat AXR. If they do not present with air fluid levels on imaging, they can be treated with oral or NG PEG solution administration. Once there has been a documented clean out and there are signs of persistent clinical improvements for more than 24 h, the patient can be discharged and should follow up with Gastroenterology.
3.4.3 Gastrograffin enema
This is a hypertonic solution of sodium meglumine diatrizoate that can be administered either orally or via naso-gastric tube or rectally.12, 38 It acts by drawing fluid into the lumen through its hypertonic nature, which in turn stimulates intestinal movement and decreases intestinal edema.55 Side effects associated with the usage of gastrografin include bowel perforation, necrotizing enterocolitis, and hypovolemic shock.12
N-acetyl cysteine (Mucomyst) administered orally has been a mucolytic treatment for CF patients with DIOS.12 However, its use has been superseded by medications such as gastrograffin.38 30 to 60 mL of the solution can be given either enterically by mouth or feeding tube and diluted in a sweet drink to mask the taste.56 It acts by reducing disulfide bonds and scavenging reactive oxygen species, which helps to break up mucus in the intestines.56, 57
Newer medications such as lubiprostone and linaclotide are used for chronic constipation and IBS-C but no data available regarding efficacy in the acute setting of DIOS.
Due to high risk of perforation, sepsis and mortality, acute severe episodes of DIOS refractory to medical treatment or presenting with impending complications might need endoscopic and surgical intervention.12, 38
3.4.4 Prophylaxis
Studies have shown that individuals who have experienced a prior DIOS episode are more likely to experience subsequent episodes.39 Therefore, prophylactic treatment should be considered through a stepwise approach. It is imperative to monitor daily laxative regime and assess stooling patterns. Parents and physicians must recognize signs and symptoms of DIOS as early intervention will help avoid morbidity and mortality.
4 CONCLUSION
In summary, Constipation and Distal Intestinal Obstruction Syndrome (DIOS) represent significant gastrointestinal (GI) challenges for People with Cystic Fibrosis (PwCF). Despite the availability of current treatment modalities, managing refractory constipation and preventing DIOS remains a challenge. This underscores the critical need for a comprehensive understanding of their clinical manifestations and pathogenesis to ensure effective diagnosis and treatment. Fortunately we now have several nonprescription and prescription medications for treating constipation in children over age of 6 and in adults and familiarity with their mechanism of action in PwCF can enhance patient care as they may oftentimes have to be combined.
This review article has focused on elucidating the complexities surrounding constipation and DIOS in CF, proposing a stepwise algorithm for their management while also acknowledging the presence of overlapping symptoms with other comorbidities. Furthermore, the necessity for randomized clinical trials to assess the efficacy of novel treatment options is highlighted, particularly those approved by the FDA for chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C), in addressing constipation in individuals with CF.
AUTHOR CONTRIBUTIONS
Pavithra Saikumar: Writing—original draft. Marisa Sadauskas: Writing—original draft. Sophia Izhar: Writing—original draft. Baha Moshiree: Writing—review and editing. Dhiren Patel: Writing—review and editing.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.
