Table 1.

Qualitative data obtained from the studies (n = 12) isolated during a systematic search of the PubMed database

			Respiratory relevant findings
Author (Year)	Aim	Design	Primary comparison	Alternative comparisons
Bachmann et al. (2009)	Investigate the influence of cachexia on fat, muscle and lung function in patients with pancreatic cancer	Non‐cachectic PDA patients Cachectic PDA patients	CC vs. non‐CC ↓ relative VC ↔ absolute VC ↔ absolute FEV1 ↔ relative FEV1
Chacon‐Cabrera et al. (2014)	Assess the effects of treatment with NF‐κB, MAPK or proteasome inhibitors on respiratory and limb muscle in cancer cachexia	Control LP07 LC LP07 LC + proteasome inhibitor LP07 LC + NF‐κB inhibitor LP07 LC + MAPK inhibitor	CC vs. control Diaphragm ↓ muscle mass ↑ protein degradation ↑ myostatin ↓ myogenin ↓ MyHC	CC + proteasome vs. CC ↔ muscle mass ↓ protein degradation ↓ myostatin ↔ myogenin ↔ MyHC	CC + NF‐κB vs. CC ↑ muscle mass ↓ protein degradation ↓ myostatin ↑ myogenin ↑ MyHC	CC + MAPK vs. CC ↑ muscle mass ↓ protein degradation ↓ myostatin ↑ myogenin ↑ MyHC
Choi et al. (2013)	Assess the validity of the Lewis lung carcinoma model and examine its effects on skeletal muscle	Control LLC	CC vs. control Diaphragm ↓ specific force
Fermoselle et al. (2013)	Explore whether cancer cachexia alters MRC complexes and oxygen uptake in respiratory and limb muscles	Control LP07 LC LP07 LC + NAC LP07 LC + NF‐κB inhibitor LP07 LC + MAPK inhibitor	CC vs. control Diaphragm ↓ muscle mass ↔ citrate synthase ↓ MRC complex I, II, IV ↓ oxygen consumption	CC + NAC vs. CC ↔ muscle mass ↔ citrate synthase ↔ MRC complex I, II, IV ↑oxygen consumption	CC + NF‐κB vs. CC ↑ muscle mass ↑ citrate synthase ↑ MRC complex I, II, IV ↑ oxygen consumption	CC + MAPK vs. CC ↑ muscle mass ↔ citrate synthase ↔ MRC complex I, II ↑ MRC complex IV ↑ oxygen consumption
Fields et al. (2019)	Examine neural involvement in cachexia‐linked respiratory insufficiency	Control C26	Normoxia ↔ V T ↑ breathing frequency ↑ ${\dot{V}}_{\mathrm{E}}$	Hypoxia ↓ V T ↔ breathing frequency ↓ ${\dot{V}}_{\mathrm{E}}$ ↓ inspiratory burst amplitude ↔ phrenic nerve firing frequency	Hypercapnia ↔ V T ↔ breathing frequency ↔ ${\dot{V}}_{\mathrm{E}}$ ↔ inspiratory burst amplitude ↔ phrenic nerve firing frequency	Maximal Chemoreflex ↔ V T ↔ breathing frequency ↔ ${\dot{V}}_{\mathrm{E}}$ ↔ inspiratory burst amplitude ↔ phrenic nerve firing frequency
Murphy et al. (2012)	Characterise functional impairments in mild and severe cachexia to inform the suitability of the C26 model	Control C26‐mild C26‐severe	CC‐mild vs. control Diaphragm ↔ specific force ↔ twitch characteristics ↓ force (fatigued)	CC‐severe vs. control ↓ specific force ↔ twitch characteristics ↓ force (fatigued)
Murphy et al. (2013)	Assess whether treatment with perindopril enhances whole body and skeletal muscle function in cancer cachexia	Control C26‐mild C26‐mild + treatment C26‐severe C26‐severe + treatment	CC‐mild vs. control Diaphragm ↓ specific force ↔ twitch characteristics ↔ specific force–freq. relationship	CC‐mild vs. perindopril ↔ specific force ↔ twitch characteristics ↔ specific force‐freq. relationship	CC‐severe vs. control ↓ specific force ↔ twitch characteristics ↓ force across force–freq. relationship	CC‐severe vs. perindopril ↔ specific force ↔ twitch characteristics ↓ force across force–freq. relationship
Nosacka et al. (2020)	Assess pathophysiological differences between limb and diaphragm muscle in cancer cachexia	Control PDAC‐PDX	Diaphragm ↓ fibre CSA ↑ extracellular space ↑ irregular shaped fibres ↑ no. mononuclear cells ↑ no. necrotic fibres	Tibialis anterior ↓ fibre CSA ↔ extracellular space ↔ fibre shape ↔ no. mononuclear cells ↔ no. necrotic fibres	Transcriptome No. genes upregulated TA vs. DIA = 30 overlap No. genes downregulated TA vs. DIA = 39 overlap
Rosa‐Caldwell et al. (2020)	Investigate signalling related to mitochondrial function, ROS production and protein synthesis during cancer cachexia development	Control – week 0 LLC – week 1 LLC – week 2 LLC – week 3 LLC – week 4	Week 1 vs. week 0 ↔ mitochondrial RCR ↔ mitochondrial content ↔ PGC‐1α ↔ ROS production ↔ SOD1, SOD2 or SOD3 ↔ FSR	Week 2 vs. week 0 ↓ mitochondrial RCR ↔ mitochondrial content ↔ PGC‐1α ↑ ROS production ↔ SOD1, SOD2 or SOD3 ↔ FSR	Week 3 vs. week 0 ↔ mitochondrial RCR ↔ mitochondrial content ↔ PGC‐1α ↔ ROS production ↔ SOD1, SOD2 or SOD3 ↔ FSR	Week 4 vs. week 0 ↓ mitochondrial RCR ↔ mitochondrial content ↔ PGC‐1α ↔ ROS production ↔ SOD1, SOD2 or SOD3 ↔ FSR
Salazar‐Degracia et al. (2018)	Assess the effects of treatment with β2 agonist formoterol on atrophy signalling pathways and muscle metabolism of limb and respiratory muscle in cancer cachexia	Control Control + formoterol CC CC + formoterol	CC vs. control Diaphragm ↓ muscle mass ↓ muscle fibre CSA ↑ muscle structure abnormalities ↑ NF‐κB activity ↑ FoxO activity ↑ myostatin levels ↓ mTOR activity levels ↓ PGC‐1α	CC + formoterol vs. control ↓ muscle mass ↔ muscle fibre CSA ↔ muscle structure abnormalities ↔ NF‐κB activity levels ↑ FoxO activity ↔ myostatin levels ↓ mTOR activity levels ↓ PGC‐1α	CC + formoterol vs. CC ↔ muscle mass ↑ muscle fibre CSA ↓ muscle structure abnormalities ↓ NF‐κB activity levels ↔ FoxO activity ↓ myostatin levels ↔ mTOR activity levels ↔ PGC‐1α
Smith et al. (2016)	Determine whether the JAK1/3 signalling pathway contributes to cancer cachexia‐mediated diaphragm muscle weakness	Control Control + JAK inhibitor C26 C26 + JAK inhibitor	CC vs. control Diaphragm ↓ specific force	CC + JAK vs. control ↔ specific force
Smuder et al. (2020)	Assess the impact of pharmacological treatment of mitochondrial dysfunction and ROS production in cancer cachexia	Control + saline Control + SS‐31 C26 + saline C26 + SS‐31	CC vs. control Diaphragm ↓ specific force ↓ fibre CSA ↓ normoxic V T ↓ normoxic ${\dot{V}}_{\mathrm{E}}$ ↓ hypoxic VT ↓ hypoxic ${\dot{V}}_{\mathrm{E}}$ ↑ ROS emission ↓ mitochondrial RCR	CC + SS‐31 vs. control ↔ specific force ↔ fibre CSA ↔ normoxic VT ↔ normoxic ${\dot{V}}_{\mathrm{E}}$ ↔ hypoxic VT ↔ hypoxic ${\dot{V}}_{\mathrm{E}}$ ↔ ROS emission ↔ mitochondrial RCR

↑, significant increase; ↓, significant decrease; ↔, no significant difference; C26, colon 26 adenocarcinoma; CC, cancer cachexia; CSA, cross‐sectional area; DIA, diaphragm; FEV1, forced expiratory volume in 1 s; FSR, fractional synthesis rate; LC, lung cancer; LLC, Lewis lung carcinoma; MRC, mitochondrial respiratory chain; NAC, N‐acetyl cysteine; PDA, pancreatic ductal adenocarcinoma; PDAC‐PDX, pancreatic ductal adenocarcinoma patient derived xenograft; RCR, respiratory control ratio; ROS, reactive oxygen species; SOD, superoxide dismutase; TA, tibialis anterior; VC, vital capacity; V _T, tidal volume; ${\dot{V}}_{\mathrm{E}}$, minute ventilation.