8.2.1. Description of clinical evidence: malnutrition

The aim of this review was to determine the prevalence of malnutrition among adults with cystic fibrosis, and the prevalence of vitamin deficiency among people of all ages. This section includes studies on adult or mixed populations or studies on vitamin deficiency with people of all ages. Please see the following section on impaired growth for studies focusing on children and young people.

We requested data to the UK CF registry on the percentage of adults with body mass index (BMI) under or over the cut-offs for normal nutritional status as outlined in the consensus document on nutritional management of cystic fibrosis published by the CF Trust in 2016 (CF Trust 2016). Data from the registry should be prioritised according to the protocol. We also looked for observational studies because they would provide data on indicators not included in the registry. We aimed to prioritise prospective cohort studies, but only included a prospective cross-sectional study and 4 retrospective studies. We prioritised studies from more relevant contexts (the UK in the first instance, then countries in Western Europe, Australia or North America). We also prioritised studies with more recent data for each indicator of malnutrition. Moreover, we prioritised studies that disaggregated data between infants, children, young people and adults; as well as studies that reported prevalence at different points in time and studies that were based on registries.

For full details see review protocol in Appendix D.

We included data obtained from the UK CF registry for the year 2015. This data referred to 5701 people with cystic fibrosis aged >16 years. In addition to these data, we included 3 studies on malnutrition defined by indicators such as BMI, height percentile or BMI percentile. One study (Moen 2011) was a prospective multicentre study conducted in Denmark, Norway and Sweden from 2003 to 2006. This study included 347 adults with cystic fibrosis. One study (Stephenson 2013) used data from the Toronto CF registry for 3 time intervals: 1985–1990, 1991–1999, and 2000–2011. This study included 909 people with cystic fibrosis attending an adult clinic. 1 study (Vieni 2013) used data from 2 centres in Italy from 2007. This study included 393 people with cystic fibrosis aged >6 years.

We included 2 retrospective studies on vitamin deficiency. One study (Chavasse 2004) used data from a CF clinic in the UK for 1999–2001. This study included 290 people with cystic fibrosis aged 1–18. One study (Rana 2014) used data from 3 paediatric centres in Australia for 2007–2010. This study included 530 people with cystic fibrosis aged ≤18 years.

8.2.2. Summary of included studies and results: malnutrition

A summary of the studies that were included in this review are presented in Table 49.

Table 49

Summary of included studies.

8.2.3. Evidence statements: malnutrition

Moderate quality evidence from the UK CF Registry with 5701 people with cystic fibrosis aged >16 found that the prevalence of those who required additional nutritional support (defined as BMI < 20 kg/m2) was 24.5% and the prevalence of overweight (defined as BMI > 25 kg/m2) was 22.2% in 2015.

High quality evidence from 1 study with 347 adults with cystic fibrosis attending 7 centres in Denmark, Norway and Sweden found that the prevalence of malnutrition defined as BMI<19.0 kg/m2 was 18% and the prevalence of malnutrition defined as BMI <18.5 kg/m2 was 13% between 2003 and 2006.

Low quality evidence from 1 study with 909 people with cystic fibrosis attending an adult clinic in Toronto found that the prevalence of underweight (defined as BMI<18.5 kg/m²) was 17%, the prevalence of overweight (defined as BMI 25–29.9 kg/m2) was 18% and the prevalence of obesity (defined as BMI≥30 kg/m2) was 3.8%, using the last recorded measurement for each person between 2000 and 2011. Using 1000 random measurements per time interval, the prevalence of underweight was 20.6% in 1985–1990, 11.6% in 1991–1999, 11.1% in 2000–2011 and the prevalence of overweight was 7.0% in 1985–1900, 15.8% in 1991–1999, and 18.4% in 2000–2011.

Low quality evidence from 1 study with 393 people with cystic fibrosis aged >6 years from 2 centres in Italy found that the prevalence of height percentile <5th was 24.4%, and the prevalence of either BMI percentile <10th or BMI <18.5 kg/m2 (depending on the age) was 35.3% in 2007.

Moderate quality evidence from 1 study with 290 people with cystic fibrosis aged 1–18 attending a clinic in the UK found that the prevalence of 25-hydroxyvitamin D (25-OHD)< 15 nmol/l was 1% and the prevalence of 25-OHD < 25 nmol/l was 6% between 1999 and 2001.

Very low quality from 1 study with 530 people with cystic fibrosis aged ≤18 years attending 3 paediatric centres in Australia found that the prevalence of vitamin A deficiency was 11.17% in 2007 and 13.13% in 2010, the prevalence of vitamin D deficiency was 22.11% in 2007 and 20.22% in 2010, the prevalence of vitamin E deficiency was 15.54% in 2007 and 13.89% in 2010. Prevalence of deficiency of 1 or more fat-soluble vitamins was 45% on first vitamin level test. Prevalence of abnormal vitamin A levels was 23.4% and of low vitamin A levels was 15% on first vitamin level test. Prevalence of abnormal vitamin 25-OHD levels was 19.8% and of low vitamin 25-OHD levels was 19% on first vitamin level test. Prevalence of abnormal vitamin E levels was 38.4% (201/523) and of low vitamin E levels was 20% (105/523) on first vitamin level test.

8.3.1. Description of clinical evidence: impaired growth

The aim of this review was to determine the prevalence of impaired growth among infants, children and young people with cystic fibrosis.

We requested data to the UK CF registry on the percentage of children and young people with BMI percentile below the cut-off for additional nutritional support or above the cut-off for overweight as outlined in the consensus document on nutritional management of cystic fibrosis published by the CF Trust in 2016. Data from the registry should be prioritised according to the protocol. We also looked for observational studies because they would provide data on indicators not included in the registry. We aimed to prioritise prospective cohort studies, but only included 1 prospective cross-sectional study and 4 retrospective studies. We prioritised studies from more relevant contexts (the UK in the first instance, then countries in Western Europe, Australia or North America). We also prioritised studies with more recent data for each indicator of impaired growth. Moreover, we prioritised studies that disaggregated data between infants, children, young people and adults; as well as studies that reported prevalence at different points in time and studies that were based on registries.

For full details see review protocol in Appendix D.

We included data obtained from the UK CF registry for the year 2015. This data referred to 3383 people with cystic fibrosis aged 2 to 16 years. In addition to these data, we included 5 studies on impaired growth. Older studies were included because they provided data on indicators or age sub-groups not covered by more recent studies. Four studies used data from the CF Foundation National Registry in the United States. One study (Heltshe 2014) used data for 2004–2009. This study included 1992 infants and children with cystic fibrosis aged 0–24 months. One study (Zhang 2013) used data from 1994–2008 to calculate pubertal peak height velocity. This study included 1862 people with cystic fibrosis aged 10 to 18 years old. One study (Lai 2008) used data from 2002. This study included 14702 people with cystic fibrosis aged less than 20 years old. One study (Zhang 2010) used data from the CF Foundation Patient Registry in the United States from 1986 to 2005. This study included 3306 people with cystic fibrosis aged 2–18.5. This study provided the most recent data relating to Himes adjusted percentiles. One study (Lucidi 2009) was a prospective multicentre study with 10 Italian CF centres from 2005 to 2006. It included 892 people with cystic fibrosis aged 1 month to 18 years.

8.3.2. Summary of included studies and results: impaired growth

A summary of the studies that were included in this review are presented in Table 50.

Table 50

Summary of included studies.

8.3.3. Evidence statements: impaired growth

Moderate quality evidence from the UK CF Registry found that the prevalence of children who required additional nutritional support (defined as BMIp<25th) was 17.3% and the prevalence of overweight (defined as BMIp>91st) was 10.1% in 2015. The same evidence found that the prevalence of young people aged 12–16 who required additional nutritional support (defined as BMIp<25th) was 27.5% and the prevalence of overweight (defined as BMIp>91st) was 5.9% in 2015. The same evidence found that the prevalence of children and young people aged 2–16 requiring additional nutritional support (defined as BMIp<25th) was 20.0% and the prevalence of overweight (defined as BMIp>91st) was 9.0%.

Moderate quality evidence from 1 study with infants and children with cystic fibrosis aged 0–24 months in the US CF Foundation Registry found that the prevalence of impaired growth at 12 months was the following between 2004 and 2009, depending on the definition used:

• weight for age <10th: 11%
• weight for age <5th: 8.3%
• weight for age <2.5th: 3.7%
• weight velocity (GUO-US) <50th: 48.1%
• weight velocity (WHO)<50th: 30.5%
• weight velocity <10th (WHO): 6.4%
• weight velocity<5th (WHO): 4.5%
• weight velocity<2.5th (WHO): 3.5%
• length for age <10th: 26.8%
• length for age <5th: 17.7%
• length for age <2.5th: 10.4%
• length velocity (GUO-US) <50th: 45.7%
• length velocity <50th (WHO): 38.4%
• length velocity <10th (WHO): 20.7%
• length velocity<5th (WHO): 13.4%
• length velocity<2.5th (WHO): 13.4%
• The same study found that the prevalence of impaired growth at 24 months was the following between 2004 and 2009, depending on the definition used:
• weight for age <10th: 6.9%
• weight for age <5th: 2.8%
• weight for age <2.5th: 1.9%
• weight velocity (GUO-US) <50th: 59.3%
• weight velocity (WHO)<50th: 51.1%
• weight velocity <10th (WHO): 18.3%
• weight velocity<5th (WHO): 12.6%
• weight velocity<2.5th (WHO): 8.2%
• length for age <10th: 24.9%
• length for age <5th: 17%
• length for age <2.5th: 11.4%
• length velocity (GUO-US) <50th: 57.4%
• length velocity <50th (WHO): 58.7%
• length velocity <10th (WHO): 30.3%
• length velocity<5th (WHO): 24.3%
• length velocity<2.5th (WHO): 19.9%

Very low quality evidence from 1 study with 14702 people aged less than 20 years old registered in the US CF Foundation Patient Registry found that the prevalence of underweight defined as either height percentile <5th or BMIp<10th or %IBW<90 was 33.0%, the prevalence of underweight defined as height percentile <5th or BMIp < 10th was 26.8%, and the prevalence of people below BMI goal defined as BMIp<50^th was 56.8% in 2002.

Moderate quality evidence from 1 study with 892 people with cystic fibrosis aged 1 month to 18 years from 10 Italian centres found that between 2005 and 2006 the prevalence of malnutrition defined as HAP<5^th was 15.4% and the prevalence of malnutrition defined as WLP<10^th was 12.9% among infants and children aged 0–2 years. The prevalence of the risk of malnutrition defined as HAP 5th–25^th was 18.3% and the prevalence of the risk of malnutrition defined as WLP 10th–25^th was 22.7% in the same age group. Among people aged 2–18 years, the prevalence of malnutrition defined as HAP<5^th was 11.8% and the prevalence of malnutrition defined as BMIp<15^th was 20.9%. The prevalence of the risk of malnutrition defined as HAP 5th-25^th was 29.3% and the prevalence of the risk of malnutrition defined as BMIp 15th-25^th was 9.6% in the same age group. The prevalence of BMIp<50^th was 54.4% in the same age group. Among people aged 10–14, the prevalence of malnutrition defined as HAP<5^th was 11.7% and the prevalence of malnutrition defined as BMIp<15^th was 20.1%. Among people aged 14–18 years, the prevalence of malnutrition defined as HAP<5^th was 21.9% and the prevalence of malnutrition defined as BMIp<15^th was 27.9%. Among people aged 0–18 years old, the prevalence of malnutrition defined as HAP<5^th was 12.2% and the prevalence of the risk of malnutrition defined as HAP 5^th-25^th was 28%.

Moderate quality evidence from a study with 3306 people with cystic fibrosis aged 2–18.5 from the CF Foundation Patient Registry of the United States found that the prevalence of impaired growth was the following between 1986 and 2005, depending on the definition used: Unadjusted height percentile <5th: 16%; unadjusted height percentile <10th: 26%; Himes adjusted height percentile <5th: 18%; Himes adjusted height percentile: <10th: 31%; CFF lower bound method: 24%.

High quality evidence from a study with 1862 people with cystic fibrosis aged 10–18 registered in the CF Foundation Patient Registry of the United States found that the prevalence of attenuated but not delayed pubertal peak velocity (magnitude <5^th percentile) was 20.8%, the prevalence of attenuated and delayed pubertal peak velocity (PHV age at 2SD later than average and magnitude <5^th percentile) was 5.3% between 1994 and 2008.

8.4.1. Description of clinical evidence: cystic fibrosis related renal disease

The aim of this review was to determine the prevalence of cystic fibrosis related renal disease among infants, children and young people with cystic fibrosis.

We extracted data from the UK CF Registry on renal failure and kidney stones. Data from the UK CF Registry should be prioritised according to the protocol, however the committee believed that the registry was likely to underreport the prevalence of renal failure because routine measurements of renal function are not very reliable; moreover it does not provide prevalence data for chronic kidney disease and acute kidney injury; therefore we also looked for observational studies on these complications. We aimed to prioritise prospective cohort studies, but only included 2 retrospective studies. We aimed to prioritise studies from more relevant contexts (the UK in the first instance, then countries in Western Europe, Australia or North America) and more recent studies.

For full details see review protocol in Appendix D.

We included data from the UK CF Registry for the year 2015 on 9587 people with cystic fibrosis. In addition to these data, we included 2 studies. One study (Quon 2011) used data from the CF Foundation Registry in the United States for 2001–2008. This study included 11912 adults with cystic fibrosis. One study (Wilcock 2015) used data from a database of an adult CF centre in the UK for 1969–2009. This study included 1532 people with cystic fibrosis.

8.4.2. Summary of included studies and results: cystic fibrosis related renal disease

A summary of the studies that were included in this review are presented in Table 51.

Table 51

Summary of included studies.

8.4.3. Evidence statements: cystic fibrosis related renal disease

Moderate quality evidence from a report on 9587 people with cystic fibrosis from the UK CF Registry found that in 2015 the prevalence of kidney stones was 0.3% amongst children and young people aged <16, 1.5% amongst young people and adults aged 16 years and over, and 1.0% amongst people of all ages.

Moderate quality evidence from a report on 9587 people with cystic fibrosis from the UK CF Registry found that in 2015 the prevalence of renal failure was 0% amongst children and young people aged 10–15, 1.0% amongst young people and adults aged 16 years and over, and 0.6% amongst people of all ages.

Moderate quality evidence from a study on 11912 people with cystic fibrosis aged 18 years and over registered in the CF Foundation Registry in the United States found that between 2001 and 2008 the mean annual prevalence of chronic kidney disease (stage 3 or greater) was 0.6% among people aged 18–25, 19.2% among people older than 55 years old, and 2.3% among people of all ages. The mean annual prevalence of stage 4 or greater CKD was 0.7% and the mean annual prevalence of stage 5 CKD was 0.6%.

Moderate quality evidence from a study on 1532 people with cystic fibrosis from the adult department of a centre in the UK found that between 1969 and 2009 the prevalence of renal problems was 5.1%; the prevalence of acute kidney injury was 1.1%; the prevalence of CKD was 0.9%.

8.5.1. Description of clinical evidence: delayed puberty

The aim of this review was to determine the prevalence of delayed puberty among people with cystic fibrosis.

The UK CF Registry did not provide prevalence data on this complication; therefore we looked for observational studies. We only identified 1 study eligible for inclusion.

For full details see review protocol in Appendix D.

One study (Zhang 2013) used data from the CF Foundation Registry in the United States for 1994–2008. This study included 1862 people with cystic fibrosis aged 10–18 years old.

8.5.2. Summary of included studies and results: delayed puberty

A summary of the studies that were included in this review are presented in Table 52.

Table 52

Summary of included studies.

8.5.3. Evidence statements: delayed puberty

High quality evidence from a study with 1862 people with cystic fibrosis aged 10–18 from the CF Foundation Patient Registry of the United States found that the prevalence of delayed but not attenuated pubertal peak velocity (PHV age at 2SD later than average) was 9.4% and the prevalence of attenuated and delayed pubertal peak velocity (PHV age at 2SD later than average and magnitude <5th percentile) was 5.3% between 1994 and 2008.

8.6.1. Description of clinical evidence: abdominal pain

The aim of this review was to determine the prevalence of abdominal pain among infants, children and young people with cystic fibrosis.

The UK CF Registry does not provide prevalence data on this complication. Therefore, we looked for relevant observational studies. However, we found no evidence for this complication.

For full details see review protocol in Appendix D.

8.6.2. Summary of included studies and results: abdominal pain

No evidence was found on the prevalence of this complication among people with cystic fibrosis.

8.6.3. Evidence statements: abdominal pain

No clinical or cost-effectiveness evidence was found on the prevalence of this complication among people with cystic fibrosis.

8.7.1. Description of clinical evidence: cystic fibrosis related diabetes

The aim of this review was to determine the prevalence of Cystic Fibrosis Related Diabetes (CFRD) amongst people with cystic fibrosis. We looked for data in the UK CF Registry 2015. This provided the prevalence of people on treatment for CFRD. This data was included because data from the UK CF Registry was prioritised according to the protocol. However only considering people on treatment would underestimate the prevalence of CFRD. Therefore we also looked for observational studies, excluding studies where CFRD was defined based on treatment use only. We aimed to prioritise prospective cohort studies, but only included retrospective studies. We prioritised studies from more relevant contexts (the UK in the first instance, then countries in Western Europe, Australia or North America). We also prioritised studies with more recent data and studies that disaggregated data between infants, children, young people and adults; as well as studies that reported prevalence at different points in time and studies that were based on registries.

We included data from the UK CF Registry for the year 2015 on 6970 people with cystic fibrosis aged ≥10 years. In addition to data from the UK CF Registry, we included 3 studies. One study (Lewis 2015) used data from the Minnesota Cystic Fibrosis database (United States) from 2008 to 2012. This study included 462 people with cystic fibrosis. One study (Moran 2009) used the same database to calculate prevalence at different points in time (1992–97, 1998–2000, 2003–2008) based on 872 people. Another study (Bell 2011) used the Australian CF registry data from 2009. This study included 2986 people with cystic fibrosis.

8.7.2. Summary of included studies and results: cystic fibrosis related diabetes

A summary of the studies that were included in this review are presented in Table 53.

Table 53

Summary of included studies.

8.7.3. Evidence statements: cystic fibrosis related diabetes

Moderate quality evidence from a report on from on 9587 people with cystic fibrosis from the UK CF Registry found that in 2015 the prevalence of people on treatment for CFRD was 10.0% among children and young people aged 10–16, 32.2% among young people and adults aged 16 years and over, and 28.0% among all people aged 10 years and over.

Moderate quality evidence from 1 study with 2986 people with cystic fibrosis from the Australian CF Registry found that om 2009 the prevalence of chronic insulin-dependent diabetes was 0.5% among infants and children aged 0–11, 13.6% among young people aged 12–17, 20.7% among adults aged 18 and over, and 10.0% among all age groups. The prevalence of intermittent insulin-dependent diabetes was 0% among infants and children aged 0–11, 1.1% among children aged 12–17, 2.3% among adults aged 18 years and over, 1.0% among all age groups.

Low quality evidence from 1 study with 462 people attending a CF centre in the United States found that the prevalence of CFRD was 48% among adults aged 20 years and over between 2008 and 2012.

Moderate quality evidence from 1 study with 872 people attending a CF centre in the United States found that the prevalence of CFRD was 20%+-2% at the end of the interval 1992–1997, 30%+-2% at the end of the interval 1998–2000, 33%+-2% at the end of the interval 2003–2008. The prevalence of CFRD in 2008 was 2% among infants and children aged less than 11 years, 19% amongst children and young people aged 11–17 and 43% among adults aged 18 years and over.

8.8.1. Description of clinical evidence: upper airways disease

The aim of this review was to determine the prevalence of upper airways disease among people with cystic fibrosis. We included data from the UK CF Registry for the year 2015 on 9587 people with cystic fibrosis. Data provided by the registry was prioritised therefore we did not include any studies from the published literature.

For full details see review protocol in Appendix D.

8.8.2. Summary of included studies and results: upper airways disease

A summary of the studies that were included in this review are presented in Table 54.

Table 54

Summary of included studies.

8.8.3. Evidence statements: Upper airways disease

Moderate quality evidence from a report on 9587 people with cystic fibrosis from the UK CF Registry found that in 2015 the prevalence of nasal polyps requiring surgery was 1.1% among children and young people aged <16, 3.1% among young people and adults aged 16 years and over, and 2.3% among people of all ages.

Moderate quality evidence from a report on 9587 people with cystic fibrosis from the UK CF Registry found that in 2015 the prevalence of sinus disease was 1.4% among children and young people aged <16, 15.4% among young people and adults aged 16 years and over, and 9.8% among people of all ages.

8.9.1. Description of clinical evidence: cystic fibrosis related musculoskeletal disorders

The aim of this review was to determine the prevalence of cystic fibrosis related musculoskeletal disorders among people with cystic fibrosis.

We extracted data from the UK CF Registry on the prevalence of arthritis and arthropathy. Data from the UK CF Registry should be prioritised according to the protocol, however, the committee believed that the registry was likely to underreport the prevalence of these complications as they are common in the general population and centres may not regard them as a cystic fibrosis specific complication. Therefore we also looked for observational studies. We aimed to prioritise prospective cohort studies but only found 1 retrospective study eligible for inclusion.

For full details see review protocol in Appendix D.

We included data from the UK CF Registry for the year 2015 on 9587 people with cystic fibrosis. In addition to these data, the included study (Watts 2009) used data from the CFF Patient Registry in the United States from 2004. This study included 22714 people with cystic fibrosis.

8.9.2. Summary of included studies and results: Cystic fibrosis related musculoskeletal disorders

A summary of the studies that were included in this review are presented in Table 55.

Table 55

Summary of included studies.

8.9.3. Evidence statements: cystic fibrosis related musculoskeletal disorders

Moderate quality evidence from a report on 9587 people with cystic fibrosis from the UK CF Registry found that in 2015 the prevalence of arthritis was 0.2% among children and young people aged <16, 2.6% among young people and adults aged 16 years and over, and 1.6% among people of all ages.

Moderate quality evidence from a report on 9587 people with cystic fibrosis from the UK CF Registry found that in 2015 the prevalence of arthropathy was 0.5% among children and young people aged <16, 8.7% among young people and adults aged 16 years and over, and 5.4% among people of all ages.

Very low quality from 1 study on 22714 people with cystic fibrosis from the CF Foundation Patient Registry in the United States found that the prevalence of bone and joint complications was 6.7% in 2004.

8.10.1. Description of clinical evidence: urinary stress incontinence

The aim of this review was to determine the prevalence of urinary stress incontinence among people with cystic fibrosis.

The UK CF Registry 2015 Annual Data Report did not provide prevalence data on this complication. Therefore, we looked for relevant observational studies. However, we found no evidence for this complication.

For full details see review protocol in Appendix D.

8.10.2. Summary of included studies and results: urinary stress incontinence

No evidence was found on the prevalence of this complication among people with cystic fibrosis.

8.10.3. Evidence statements: urinary stress incontinence

No evidence was found on the prevalence of this complication among people with cystic fibrosis.

8.11.1. Description of clinical evidence: reduced bone mineral density

The aim of this review was to determine the prevalence of reduced bone mineral density among people with cystic fibrosis.

We extracted data from the UK CF Registry on the prevalence of osteopenia, osteoporosis and bone fractures. Data from the UK CF Registry should be prioritised according to the protocol, however, the committee believed that the registry was likely to underreport the prevalence of reduced bone mineral density as these complications can only be diagnosed by DXA scan for which the take-up of these is not good, so many cases will be undiscovered. Therefore we also looked for observational studies on this complication. We aimed to prioritise prospective cohort studies, but only included 2 retrospective studies. We aimed to prioritise studies from more relevant contexts (the UK in the first instance, then countries in Western Europe, Australia or North America) and more recent studies but only 2 studies, both on data from 2009, were eligible for inclusion.

For full details see review protocol in Appendix D.

We included data from the UK CF Registry for the year 2015 on 9587 people with cystic fibrosis. In addition to this data, we included 2 studies. One study (Bell 2011) used data from the Australian CF registry for 2009. It included 2986 people with cystic fibrosis. One study (Somerville 2013) used data from the CF Registry of Ireland. It included 859 people with cystic fibrosis.

8.11.2. Summary of included studies and results: reduced bone mineral density

A summary of the studies that were included in this review are presented in Table 56.

Table 56

Summary of included studies.

8.11.3. Evidence statements: reduced bone mineral density

• Moderate quality evidence from a report on 9587 people with cystic fibrosis from the UK CF Registry found that in 2015 the prevalence of osteopenia was 0.9% among children and young people aged <16, 22.0% among young people and adults aged 16 years and over, and 13.5% among people of all ages.
• Moderate quality evidence from a report on 9587 people with cystic fibrosis from the UK CF Registry found that in 2015 the prevalence of osteoporosis was 0% among children and young people aged <16, 8.8% among young people and adults aged 16 years and over, and 5.3% among people of all ages.
• Moderate quality evidence from a report on 9587 people with cystic fibrosis from the UK CF Registry found that in 2015 the prevalence of bone fractures was 0.4% among children and young people aged <16, 0.6% among young people and adults aged 16 years and over, and 0.5% among people of all ages.
• Moderate quality evidence from a study on 2986 people with cystic fibrosis from the Australian CF registry found that in 2009 the prevalence of osteopenia was 0.3% among infants and children aged 0–11, 3.3% among young people aged 12–17, 25.0% among adults, 9.2% among people of all ages. The prevalence of osteoporosis was 0.2% among infants and children aged 0–11, 1.3% among young people aged 12–17, 9.5% among adults, 3.7% among people of all ages. The prevalence of fractures was 0% among infants and children aged 0–11, 0.4% among young people aged 12–17, 1.3% among adults, 0.5% among people of all ages.
• Low quality evidence from a study on 859 people with cystic fibrosis from the CF Registry of Ireland found that in 2009 the prevalence of osteopenia or osteoporosis was 5.5% among people aged <18 years, and 42.7% among people aged ≥18 years.

8.12.1. Description of clinical evidence: cystic fibrosis related liver disease

The aim of this review was to determine the prevalence of cystic fibrosis related liver disease among people with cystic fibrosis. We included data from the UK CF Registry for the year 2015 on 9587 people with cystic fibrosis. The data provided by the registry was prioritised therefore we did not include any studies from the published literature.

For full details see review protocol in Appendix D.

8.12.2. Summary of included studies and results: cystic fibrosis related liver disease

A summary of the studies that were included in this review are presented in Table 57.

Table 57

Summary of included studies.

8.12.3. Evidence statements: cystic fibrosis related liver disease

Moderate quality evidence from a report on 9587 people with cystic fibrosis from the UK CF Registry found that in 2015 the prevalence of raised liver enzymes was 6.9% among children and young people aged <16, 14.8% among young people and adults aged 16 years and over, and 11.6% among people of all ages.

Moderate quality evidence from a report on 9587 people with cystic fibrosis from the UK CF Registry found that in 2015 the prevalence of liver disease was 8.8% among children and young people aged <16, 18.0% among young people and adults aged 16 years and over, and 14.3% among people of all ages.

Moderate quality evidence from a report on 9587 people with cystic fibrosis from the UK CF Registry found that in 2015 the prevalence of cirrhosis with no portal hypertension was 0.7% among children and young people aged <16, 1.6% among young people and adults aged 16 years and over, and 1.2% among people of all ages.

Moderate quality evidence from a report on 9587 people with cystic fibrosis from the UK CF Registry found that in 2015 the prevalence of cirrhosis with portal hypertension was 0.7% among children and young people aged <16, 2.4% among young people and adults aged 16 years and over, and 1.7% among people of all ages.

8.13.1. Description of clinical evidence: infertility

The aim of this review was to determine the prevalence of infertility among people with cystic fibrosis.

The UK CF Registry does not provide prevalence data on this complication. Therefore, we looked for relevant observational studies. However, we found no evidence for this complication.

For full details see review protocol in Appendix D.

8.13.2. Summary of included studies and results: infertility

No evidence was found on the prevalence of this complication among people with cystic fibrosis.

8.13.3. Evidence statements: infertility

No evidence was found on the prevalence of this complication among people with cystic fibrosis.

8.14.1. Description of clinical evidence: Distal Intestinal Obstruction Syndrome (DIOS)

The aim of this review was to determine the prevalence of distal intestinal obstruction syndrome among people with cystic fibrosis.

The UK CF Registry provided data on intestinal obstruction, rather than on distal intestinal obstruction syndrome; therefore we also looked for observational studies on this complication. We aimed to prioritise prospective cohort studies, but only included 1 retrospective study. We prioritised studies from more relevant contexts (the UK in the first instance, then countries in Western Europe, Australia or North America). We also requested data to the registry on intestinal obstruction disaggregated by a history of meconium ileus, because the committee agreed that prevalence may vary considerably between people with or without a history of meconium ileus.

For full details see review protocol in Appendix D.

We included data from the UK CF Registry for the year 2015 on 9587 people with cystic fibrosis. In addition to these data, we included 1 study. This study (Wiedemann 2001) used data from the CF Quality Assurance Project Registry for 1997. This study included 3448 people with cystic fibrosis.

8.14.2. Summary of included studies and results: Distal Intestinal Obstruction Syndrome (DIOS)

A summary of the studies that were included in this review are presented in Table 58.

Table 58

Summary of included studies.

8.14.3. Evidence statements: Distal Intestinal Obstruction Syndrome (DIOS)

Moderate quality evidence from a report on 9587 people with cystic fibrosis from the UK CF Registry found that in 2015 the prevalence of intestinal obstruction was 3.0% among children and young people aged <16, 7.4% amongst young people and adults aged 16 years and over, and 5.6% amongst people of all ages.

Moderate quality evidence from the UK CF Registry with 9587 people found that in 2015 the prevalence of intestinal obstruction was 6.4% among children and young people aged <16 with a diagnosis of meconium ileus, and 2.3% among children and young people aged <16 without a diagnosis of meconium ileus. The same evidence found that the prevalence of intestinal obstruction was 13.9% among people aged ≥16 with a diagnosis of meconium ileus and 6.3% among people aged ≥16 without a diagnosis of meconium ileus.

Low quality evidence from a study on 3448 people with cystic fibrosis from the Quality Assurance Project registry in Germany found that in 1997 prevalence of DIOS was 3.0% among children and young people, 3.5% among adults, and 3.2% among all ages.

8.15.1. Description of clinical evidence: meconium ileus

The aim of this review was to determine the prevalence of meconium ileus among people with cystic fibrosis. We included data from the UK CF Registry for the year 2015 on 9587 people with cystic fibrosis. The data provided by the registry was prioritised therefore we did not include any studies from the published literature.

For full details see review protocol in Appendix D.

8.15.2. Summary of included studies and results: meconium ileus

A summary of the studies that were included in this review are presented in Table 59.

Table 59

Summary of included studies.

8.15.3. Evidence statements: meconium ileus

Moderate quality evidence from a report on 9587 people with cystic fibrosis from the UK CF Registry (year 2015) found that meconium ileus had occurred in 16.7% of children and young people aged <16, 14.2% of young people and adults aged 16 years and over, and 15.2% of people of all ages.

8.17.1. Relative value placed on the outcomes considered

The committee agreed that the prevalence of complications of cystic fibrosis was a critical outcome.

8.17.2. Consideration of clinical benefits and harms

8.17.3. Consideration of economic benefits and harms

This was an epidemiological review question and economic analysis to assess cost-effectiveness is not applicable as it does not involve a comparison of competing alternatives. Even so, the assessment, monitoring, referral and management of the comorbidities all have cost implications.

The committee recognised that if complications are not identified and management appropriately they can negatively impact on wellbeing, function and participation and increase their risk of further complications leading to additional treatment costs and reductions in quality of life. Therefore, knowing the prevalence of important complications may lead to increased vigilance and thus more timely management and has therefore, indirectly, potentially important resource implications. Estimating the costs to manage those complications would go beyond the scope of the guideline, but it was clear from the committee that such costs would offset the potential downstream costs from delayed or inappropriate management.

8.17.4. Quality of evidence

This was a prevalence review, therefore the quality assessment with GRADE was not performed. The quality of the studies was assessed with the checklist by Munn et al. 2014. It was often unclear from the evidence how a condition was diagnosed whether objective, standard criteria were used for the measurement of the condition or whether the condition was measured reliably. Moreover, some of the evidence did not disaggregate data by age groups.

8.17.5. Other considerations

The committee discussed whether people with cystic fibrosis may feel overwhelmed if presented with a long list of complications they are at risk of. However they agreed that people with cystic fibrosis have the right to receive all the available information on their condition. Moreover, the committee noted that the risk for each individual largely depends on management, this should be made clear in conversations with people with cystic fibrosis.

No equality issues were identified by the committee for this review question.

The committee agreed a research recommendation was not needed. They noted that there was sufficient awareness of both common and rarer complications of cystic fibrosis. It was also felt that there are robust reporting mechanisms (UK CF Registry) should the prevalence of certain complications change in the future. As people with cystic fibrosis survive longer they are more likely to present with problems associated with organ damage such as retinopathy or kidney problems in those who have diabetes. However, these are complications that are well established in the wider health-care setting and there are no specific cystic fibrosis-related treatments.

8.17.6. Key conclusions

The guideline developers concluded that health care professionals should explain to each person with cystic fibrosis and their family members or carers, as appropriate, what complications they are at risk of, taking into account each individual’s clinical risk factors. Depending on the evidence available for each complication and the individual risk factors, it may be appropriate to either use the terms common or less common, or provide a numerical estimate.