Nutrition in Patients with Idiopathic Pulmonary Fibrosis: Critical Issues Analysis and Future Research Directions

Faverio, Paola; Bocchino, Marialuisa; Caminati, Antonella; Fumagalli, Alessia; Gasbarra, Monica; Iovino, Paola; Petruzzi, Alessandra; Scalfi, Luca; Sebastiani, Alfredo; Stanziola, Anna Agnese; Sanduzzi, Alessandro

doi:10.3390/nu12041131

Cited by 38 publications

(44 citation statements)

References 101 publications

(146 reference statements)

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“…Patients aged ≥ 75 years had a lower mean weight at baseline than patients aged < 75 years, and weight loss was reported as an adverse event by a higher proportion of patients in the older age group. This suggests that in the most elderly patients, clinicians need to be particularly mindful of weight loss as an adverse event and ensure that gastrointestinal events are managed effectively and nutritional interventions provided where needed [ 21 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis who are elderly or have comorbidities

Glaspole¹,

Bonella²,

Bargagli³

et al. 2021

Respir Res

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Background Idiopathic pulmonary fibrosis (IPF) predominantly affects individuals aged > 60 years who have several comorbidities. Nintedanib is an approved treatment for IPF, which reduces the rate of decline in forced vital capacity (FVC). We assessed the efficacy and safety of nintedanib in patients with IPF who were elderly and who had multiple comorbidities. Methods Data were pooled from five clinical trials in which patients were randomised to receive nintedanib 150 mg twice daily or placebo. We assessed outcomes in subgroups by age < 75 versus ≥ 75 years, by < 5 and ≥ 5 comorbidities, and by Charlson Comorbidity Index (CCI) ≤ 3 and > 3 at baseline. Results The data set comprised 1690 patients. Nintedanib reduced the rate of decline in FVC (mL/year) over 52 weeks versus placebo in patients aged ≥ 75 years (difference: 105.3 [95% CI 39.3, 171.2]) (n = 326) and < 75 years (difference 125.2 [90.1, 160.4]) (n = 1364) (p = 0.60 for treatment-by-time-by-subgroup interaction), in patients with < 5 comorbidities (difference: 107.9 [95% CI 65.0, 150.9]) (n = 843) and ≥ 5 comorbidities (difference 139.3 [93.8, 184.8]) (n = 847) (p = 0.41 for treatment-by-time-by-subgroup interaction) and in patients with CCI score ≤ 3 (difference: 106.4 [95% CI 70.4, 142.4]) (n = 1330) and CCI score > 3 (difference: 129.5 [57.6, 201.4]) (n = 360) (p = 0.57 for treatment-by-time-by-subgroup interaction). The adverse event profile of nintedanib was generally similar across subgroups. The proportion of patients with adverse events leading to treatment discontinuation was greater in patients aged ≥ 75 years than < 75 years in both the nintedanib (26.4% versus 16.0%) and placebo (12.2% versus 10.8%) groups. Similarly the proportion of patients with adverse events leading to treatment discontinuation was greater in patients with ≥ 5 than < 5 comorbidities (nintedanib: 20.5% versus 15.7%; placebo: 12.1% versus 10.0%). Conclusions Our findings suggest that the effect of nintedanib on reducing the rate of FVC decline is consistent across subgroups based on age and comorbidity burden. Proactive management of adverse events is important to reduce the impact of adverse events and help patients remain on therapy. Trial registration: ClinicalTrials.gov NCT00514683, NCT01335464, NCT01335477, NCT02788474, NCT01979952.

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis who are elderly or have comorbidities

Glaspole¹,

Bonella²,

Bargagli³

et al. 2021

Respir Res

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“…Various studies found that nutritional abnormalities, such as low body mass index (BMI), body weight loss, and vitamin D deficiency, seem to have negative prognostic significance in patients with IPF [ 178 ]. Several factors may have a negative impact on nutritional status in IPF patients, including an increased respiratory muscle load, the coexistence of hypoxemia, and physical inactivity leading to dynapenia (low muscle strength).…”

Section: The Importance Of Comorbidities and Medical Conditions Assocmentioning

confidence: 99%

“…The two currently available antifibrotic drugs nintedanib and pirfenidone can cause adverse events that may interfere with food intake and absorption, including diarrhoea, nausea and appetite loss [ 178 ].…”

Section: The Importance Of Comorbidities and Medical Conditions Assocmentioning

confidence: 99%

Idiopathic pulmonary fibrosis beyond the lung: understanding disease mechanisms to improve diagnosis and management

et al. 2021

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Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disorder with an estimated median survival time of 3–5 years after diagnosis. This condition occurs primarily in elderly subjects, and epidemiological studies suggest that the main risk factors, ageing and exposure to cigarette smoke, are associated with both pulmonary and extrapulmonary comorbidities (defined as the occurrence of two or more disorders in a single individual). Ageing and senescence, through interactions with environmental factors, may contribute to the pathogenesis of IPF by various mechanisms, causing lung epithelium damage and increasing the resistance of myofibroblasts to apoptosis, eventually resulting in extracellular matrix accumulation and pulmonary fibrosis. As a paradigm, syndromes featuring short telomeres represent archetypal premature ageing syndromes and are often associated with pulmonary fibrosis. The pathophysiological features induced by ageing and senescence in patients with IPF may translate to pulmonary and extrapulmonary features, including emphysema, pulmonary hypertension, lung cancer, coronary artery disease, gastro-oesophageal reflux, diabetes mellitus and many other chronic diseases, which may lead to substantial negative consequences in terms of various outcome parameters in IPF. Therefore, the careful diagnosis and treatment of comorbidities may represent an outstanding chance to improve quality of life and survival, and it is necessary to contemplate all possible management options for IPF, including early identification and treatment of comorbidities.

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“…Different studies have found that obesity is a common comorbidity of IPF [38,39]. Lower body mass index (BMI) and body weight loss seemed to be related to poor outcomes [40]. Altogether, the convergence of genetic and phenotype-level results suggested that metabolic dysregulation might be a critical contributor to the pathogenesis of IPF [41].…”

Section: Discussionmentioning

confidence: 99%

Integrative Analyses Reveal Novel Disease-associated Loci and Genes for Idiopathic Pulmonary Fibrosis

Chen

Zhang

Adams

et al. 2021

Preprint

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Background: Although genome-wide association studies have identified many genomic regions associated with idiopathic pulmonary fibrosis (IPF), the causal genes and functions remain largely unknown. Many bulk and single-cell expression data have become available for IPF, and there is increasing evidence suggesting a shared genetic basis between IPF and other diseases. Methods: By leveraging shared genetic information and transcriptome data, we conducted an integrative analysis to identify novel genes for IPF. We first considered observed phenotypes, polygenic risk scores, and genetic correlations to investigate associations between IPF and other traits in the UK Biobank. We then performed local genetic correlation analysis and cross-tissue transcriptome-wide association analysis (TWAS) to identify IPF genes. We further prioritized genes using bulk and single-cell gene expression data. Findings: We identified 25 traits correlated with IPF on the phenotype level and seven traits genetically correlated with IPF. Using local genetic correlation, we identified 12 candidate genes across 14 genomic regions, including the POT1 locus (p-value = 4.1E-4), which contained variants with protective effects on lung cancer but increasing IPF risk. Using TWAS, we identified 36 genes, including 12 novel genes for IPF. Annotation-stratified heritability estimation and differential expression analysis of downstream-regulated genes suggested regulatory roles of two candidate genes, MAFK and SMAD2, on IPF. Interpretation: Our integrative analysis identified new genes for IPF susceptibility and expanded the understanding of the complex genetic architecture of IPF. Funding: NIHR Leicester Biomedical Research Centre, Three Lakes Partners, the National Institutes of Health, the National Science Foundation, U01HL145567, and UH2HL123886.

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Nutrition in Patients with Idiopathic Pulmonary Fibrosis: Critical Issues Analysis and Future Research Directions

Cited by 38 publications

References 101 publications

Efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis who are elderly or have comorbidities

Efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis who are elderly or have comorbidities

Idiopathic pulmonary fibrosis beyond the lung: understanding disease mechanisms to improve diagnosis and management

Integrative Analyses Reveal Novel Disease-associated Loci and Genes for Idiopathic Pulmonary Fibrosis

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