Diferentes tipos de corticosteroides intranasales para la rinosinusitis crónica
Appendices
Appendix 1. Search strategies
| CENTRAL | Ovid MEDLINE |
| #1 MeSH descriptor: [Sinusitis] explode all trees #2 MeSH descriptor: [Rhinitis] this term only #3 MeSH descriptor: [Rhinitis, Atrophic] this term only #4 MeSH descriptor: [Rhinitis, Vasomotor] this term only #5 MeSH descriptor: [Paranasal Sinus Diseases] this term only #6 MeSH descriptor: [Paranasal Sinuses] explode all trees #7 rhinosinusitis or nasosinusitis or pansinusitis or ethmoiditis or sphenoiditis #8 kartagener* near syndrome* #9 inflamm* near sinus* #10 (maxilla* or frontal*) near sinus* #11 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 #12 MeSH descriptor: [Chronic Disease] explode all trees #13 MeSH descriptor: [Recurrence] explode all trees #14 chronic or persis* or recurrent* #15 #12 or #13 or #14 #16 #11 and #15 #17 CRSsNP #18 (sinusitis or rhinitis) near (chronic or persis* or recurrent*) #19 #16 or #17 or #18 #20 MeSH descriptor: [Nasal Polyps] explode all trees #21 MeSH descriptor: [Nose] explode all trees #22 MeSH descriptor: [Nose Diseases] explode all trees #23 #21 or #22 #24 MeSH descriptor: [Polyps] explode all trees #25 #23 and #24 #26 (nose or nasal or rhino* or rhinitis or sinus* or sinonasal) near (papilloma* or polyp*) #27 rhinopolyp* or CRSwNP #28 #19 or #20 or #25 or #26 or #27 #29 MeSH descriptor: [Steroids] explode all trees #30 MeSH descriptor: [Adrenal Cortex Hormones] explode all trees #31 MeSH descriptor: [Glucocorticoids] explode all trees #32 MeSH descriptor: [Anti‐Inflammatory Agents] explode all trees #33 MeSH descriptor: [Anti‐Inflammatory Agents, Non‐Steroidal] explode all trees #34 #32 not #33 #35 steroid* or glucocorticoid* or corticosteroid* or glucosteroid* or cyclocosteroid* #36 beclomethasone or beclometasone or beclamet or beclocort or becotide #37 betamethasone or betadexamethasone or flubenisolone or celeston* or cellestoderm or betnelan or oradexon #38 dexamethasoneor dexameth or dexone or dexametasone or decadron or dexasone or hexadecadron or hexadrol or methylfluorprednisolone or millicorten #39 flunisolide or fluticasone or hydrocortisone or cortisol or cortifair or cortril or hyrocortone or cortef or epicortisol or efcortesol or Cortisone #40 methylprednisolone or medrol or metripred or urbason #41 mometasone or prednisolone or precortisyl or deltacortril or deltastab or prednesol or deltasone or prednisone or cortan or liquid next pred or meticorten #42 paramethasone or triamcinolone or aristocort or volon or atolone or kenacort or orasone or panasol or prednicen #43 corticoid* or betamethason* or betamethasone or hydrocortison* or celesto* or dexamethason* or hexadecadrol or budesonid* or horacort or pulmicort or rhinocort or methylfluorprednisolone or flunisolid* or nasalide or fluticason* or flonase or flounce or mometason* or nasonex or triamclinolon* or nasacort or tri next nasal or aristocort or Ciclesonide #44 #29 or #30 or #31 or #34 or #35 or #36 or #37 or #38 or #39 or #40 or #41 or #42 or #43 #45 #28 and #44 | 1 exp Sinusitis/ 2 paranasal sinus diseases/ or rhinitis/ or rhinitis, atrophic/ or rhinitis, vasomotor/ 3 exp Paranasal Sinuses/ 4 (rhinosinusitis or nasosinusitis or pansinusitis or ethmoiditis or sphenoiditis).ab,ti. 5 (kartagener* adj3 syndrome*).ab,ti. 6 (inflamm* adj5 sinus*).ab,ti. 7 ((maxilla* or frontal*) adj3 sinus*).ab,ti. 8 1 or 2 or 3 or 4 or 5 or 6 or 7 9 exp chronic disease/ 10 exp Recurrence/ 11 (chronic or persis* or recurrent*).ab,ti. 12 9 or 10 or 11 13 8 and 12 14 CRSsNP.ab,ti. 15 ((sinusitis or rhinitis) adj3 (chronic or persis* or recurrent*)).ab,ti. 16 13 or 14 or 15 17 exp Nasal Polyps/ 18 exp Nose/ or exp Nose Diseases/ 19 exp Polyps/ 20 18 and 19 21 ((nose or nasal or rhino* or rhinitis or sinus* or sinonasal) adj3 (papilloma* or polyp*)).ab,ti. 22 (rhinopolyp* or CRSwNP).ab,ti. 23 16 or 17 or 20 or 21 or 22 24 exp Steroids/ 25 exp Adrenal Cortex Hormones/ 26 exp Glucocorticoids/ 27 exp Anti‐Inflammatory Agents/ 28 exp Anti‐Inflammatory Agents, Non‐Steroidal/ 29 27 not 28 30 (steroid* or glucocorticoid* or corticosteroid* or glucosteroid* or cyclocosteroid* orbeclomethasone or beclometasone or beclamet or beclocort or becotide or betamethasone or betadexamethasone or flubenisolone or celeston* or cellestoderm or betnelan or oradexon or dexamethasone or dexameth or dexone or dexametasone or decadron or dexasone or hexadecadron or hexadrol or methylfluorprednisolone or millicorten or flunisolide or fluticasone or hydrocortisone or cortisol or cortifair or cortril or hyrocortone or cortef or epicortisol or efcortesol or Cortisone or methylprednisolone or medrol or metripred or urbason or mometasone or prednisolone or precortisyl or deltacortril or deltastab or prednesol or deltasone or prednisone or cortan or liquid next pred or meticorten or paramethasone or triamcinolone or aristocort or volon or atolone or kenacort or orasone or panasol or prednicen).ab,ti. 31 (corticoid* or betamethason* or betamethasone or hydrocortison* or celesto* or dexamethason* or hexadecadrol or budesonid* or horacort or pulmicort or rhinocort or methylfluorprednisolone or flunisolid* or nasalide or fluticason* or flonase or flounce or mometason* or nasonex or triamclinolon* or nasacort or (tri adj3 nasal) or aristocort or Ciclesonide).ab,ti. 32 24 or 25 or 26 or 29 or 30 or 31 33 23 and 32 |
| Ovid Embase | Trial registries (via CRS) |
| 1 exp sinusitis/ or paranasal sinus disease/ 2 atrophic rhinitis/ or chronic rhinitis/ or rhinosinusitis/ or vasomotor rhinitis/ 3 exp paranasal sinus/ 4 (rhinosinusitis or nasosinusitis or pansinusitis or ethmoiditis or sphenoiditis).tw. 5 (kartagener* adj3 syndrome*).tw. 6 (inflamm* adj5 sinus*).tw. 7 ((maxilla* or frontal*) adj3 sinus*).tw. 8 1 or 2 or 3 or 4 or 5 or 6 or 7 9 exp chronic disease/ 10 exp recurrent disease/ 11 (chronic or persis* or recurrent*).tw. 12 9 or 10 or 11 13 8 and 12 14 CRSsNP.tw. 15 ((sinusitis or rhinitis) adj3 (chronic or persis* or recurrent*)).tw. 16 13 or 14 or 15 17 exp nose polyp/ 18 exp nose disease/ or exp nose/ 19 exp polyp/ 20 18 and 19 21 ((nose or nasal or rhino* or rhinitis or sinus* or sinonasal) adj3 (papilloma* or polyp*)).tw. 22 (rhinopolyp* or CRSwNP).tw. 23 16 17 or or 20 or 21 or 22 24 exp *corticosteroid/ 25 exp steroid/ 26 exp antiinflammatory agent/ 27 exp nonsteroid antiinflammatory agent/ 28 26 not 27 29 (steroid* or glucocorticoid* or corticosteroid* or glucosteroid* or cyclocosteroid* or beclomethasone or beclometasone or beclamet or beclocort or becotide or betamethasone or betadexamethasone or flubenisolone or celeston* or cellestoderm or betnelan or oradexon or dexamethasone or dexameth or dexone or dexametasone or decadron or dexasone or hexadecadron or hexadrol or methylfluorprednisolone or millicorten or flunisolide or fluticasone or hydrocortisone or cortisol or cortifair or cortril or hyrocortone or cortef or epicortisol or efcortesol or Cortisone or methylprednisolone or medrol or metripred or urbason or mometasone or prednisolone or precortisyl or deltacortril or deltastab or prednesol or deltasone or prednisone or cortan or liquid next pred or meticorten or paramethasone or triamcinolone or aristocort or volon or atolone or kenacort or orasone or panasol or prednicen).tw. 30 24 or 28 or 29 31 23 and 30 | ClinicalTrials.gov Condition: rhinitis OR sinusitis OR rhinosinusitis OR (nose AND polyp*) OR (nasal AND polyp*) OR CRSsNP OR CRSwNP OR CRS ICTRP Title: rhinitis OR sinusitis OR rhinosinusitis OR CRSsNP OR CRSwNP OR CR OR All: (nose AND polyp*) OR (nasal AND polyp*) NB These searches were run from 1 March 2015 to 11 August 2015, when these terms were last searched to populate the Cochrane ENT trials register in CRS |
Appendix 2. Data extraction form
| REF ID: | Study title: |
| Date of extraction: | Extracted by: |
| General comments/notes (internal for discussion): |
| Flow chart of trial | ||
| Group A (Intervention) | Group B (Comparison) | |
| No. of people screened | ||
| No. of participants randomised ‐ all | ||
| No. randomised to each group | ||
| No. receiving treatment as allocated | ||
| No. not receiving treatment as allocated ‐ Reason 1 ‐ Reason 2 | ||
| No. dropped out (no follow‐up data for any outcome available) | ||
| No. excluded from analysis1 (for all outcomes) ‐ Reason 1 ‐ Reason 2 | ||
| 1This should be the people who received the treatment and were therefore not considered 'drop‐outs' but were excluded from all analyses (e.g. because the data could not be interpreted or the outcome was not recorded for some reason). | ||
| Information to go into 'Characteristics of included studies' table | |
| Methods | X arm, double/single/non‐blinded, [multicentre] parallel‐group/cross‐over/cluster‐RCT, with x duration of treatment and x duration of follow‐up |
| Participants | Location: country, no of sites etc. Setting of recruitment and treatment: Sample size:
Participant (baseline) characteristics:
Other important effect modifiers, if applicable (e.g. aspirin sensitivity, comorbidities of asthma): Inclusion criteria:[state diagnostic criteria used for CRS, polyps score if available] |
| Interventions | Intervention (n = x): drug name, method of administration, dose per day/frequency of administration, duration of treatment Comparator group (n = y): Use of additional interventions (common to both treatment arms): |
| Outcomes | Outcomes of interest in the review: Primary outcomes:
Secondary outcomes:
Other outcomes reported by the study:
|
| Funding sources | 'No information provided'/'None declared'/State source of funding |
| Declarations of interest | 'No information provided'/'None declared'/State conflict |
| Notes | |
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Quote: "…" Comment: | |
| Allocation concealment (selection bias) | Quote: "…" Comment: | |
| Blinding of participants and personnel (performance bias) | Quote: "…" Comment: | |
| Blinding of outcome assessment (detection bias) | Quote: "…" Comment: | |
| Incomplete outcome data (attrition bias) | Quote: "…" Comment: | |
| Selective reporting (reporting bias) | Quote: "…" Comment: | |
| Other bias (see section 8.15) Insensitive/non‐validated instrument? | Quote: "…" Comment: | |
| Other bias (see section 8.15) | Quote: "…" Comment: |
| Findings of study: continuous outcomes | |||||||
| Results (continuous data table) | |||||||
| Outcome | Group A | Group B | Other summary stats/Notes | ||||
| Mean | SD | N | Mean | SD | N | Mean difference (95% CI), P values etc. | |
| Disease‐specific HRQL (instrument name/range) Time point: | |||||||
| Generic HRQL (instrument name/range) Time point: | |||||||
| Symptom score (overall) (instrument name/range) Time point: | |||||||
| Added total ‐ if scores reported separately for each symptom (range) Time point: | |||||||
| Nasal blockage/obstruction/congestion (instrument name/range) | |||||||
| Nasal discharge (instrument name/range) | |||||||
| Facial pain/pressure (instrument name/range) | |||||||
| Smell (reduction) (instrument name/range) | |||||||
| Headache (instrument name/range) | |||||||
| Cough (in children) (instrument name/range) | |||||||
| Polyp size (instrument name/range) | |||||||
| CT score (instrument name/range) | |||||||
| Comments: | |||||||
| Results (dichotomous data table) | ||||||
| Outcome | Applicable review/intervention | Group A | Group B | Other summary stats/notes | ||
| No. of people with events | No. of people analysed | No. of people with events | No. of people analysed | P values, RR (95% CI), OR (95% CI) | ||
| Epistaxis/nose bleed | INCS Saline irrigation | |||||
| Local irritation (sore throat, oral thrush, discomfort) | INCS Saline irrigation | |||||
| Osteoporosis (minimum 6 months) | INCS | |||||
| Stunted growth (children, minimum 6 months) | INCS | Can also be measured as average height | ||||
| Mood disturbances | OCS | |||||
| Gastrointestinal disturbances (diarrhoea, nausea, vomiting, stomach irritation) | OCS Antibiotics | |||||
| Insomnia | OCS | |||||
| Osteoporosis (minimum 6 months) | INCS OCS | |||||
| Discomfort | Saline irrigation | |||||
| Skin irritation | Antibiotics | |||||
| Anaphylaxis or other serious allergic reactions such as Stevens‐Johnson | Antibiotics | |||||
| Comments: | ||||||
Appendix 3. Forest plots
Please see Figure 4; Figure 5.
Forest plot of comparison: 1 High‐dose versus low‐dose intranasal corticosteroids, outcome: 1.1 Disease severity ‐ overall symptoms, measured as average change from baseline at 4 months (range 0 to 3).
Forest plot of comparison: 1 High‐dose versus low‐dose intranasal corticosteroids, outcome: 1.2 Disease severity ‐ individual symptoms, measured as average change from baseline at 4 months (range 0 to 3).
Process for sifting search results and selecting studies for inclusion.
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
Forest plot of comparison: 1 High‐dose versus low‐dose intranasal corticosteroids, outcome: 1.1 Disease severity ‐ overall symptoms, measured as average change from baseline at 4 months (range 0 to 3).
Forest plot of comparison: 1 High‐dose versus low‐dose intranasal corticosteroids, outcome: 1.2 Disease severity ‐ individual symptoms, measured as average change from baseline at 4 months (range 0 to 3).
Comparison 1 High‐dose versus low‐dose intranasal corticosteroids, Outcome 1 Disease severity ‐ overall symptoms, measured as average change from baseline at 4 months (range 0 to 3).
Comparison 1 High‐dose versus low‐dose intranasal corticosteroids, Outcome 2 Disease severity ‐ individual symptoms, measured as average change from baseline at 4 months (range 0 to 3).
Comparison 1 High‐dose versus low‐dose intranasal corticosteroids, Outcome 3 Adverse effects: epistaxis.
Comparison 1 High‐dose versus low‐dose intranasal corticosteroids, Outcome 4 Adverse effects: local irritation.
Comparison 1 High‐dose versus low‐dose intranasal corticosteroids, Outcome 5 Nasal polyps size, measured as change from baseline (0 to 3 range scale) at 4 months.
Comparison 1 High‐dose versus low‐dose intranasal corticosteroids, Outcome 6 Nasal polyps ‐ proportion with improvement at 12 weeks.
| Different types of intranasal corticosteroid molecules for chronic rhinosinusitis | ||||||
| Patient or population: chronic rhinosinusitis (all studies recruited patients with bilateral polyps) | ||||||
| Outcomes № of participants | Relative effect (95%) | Anticipated absolute effects* (95% CI) | Quality | What happens | ||
| Low‐dose intranasal corticosteroids | High‐dose intranasal corticosteroids | Difference | ||||
| Disease‐specific health‐related quality of life | Not measured | Impact unknown | ||||
| Disease severity ‐ overall symptoms
| — |
| ⊕⊝⊝⊝ | No differences observed but evidence was too low quality to draw a conclusion | ||
| Adverse events: epistaxis
| — |
| ⊕⊝⊝⊝ | Unclear whether the risk of epistaxis varies for different types of steroid molecules | ||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Studies were either very small (n = 20 and n = 26) and had important drop‐outs or were only reported as an abstract with inadequate information available (n = 100). We considered all studies to be at unclear to high risk of selective reporting and attrition bias. The evidence was very low quality due to very serious imprecision and very serious risk of bias concerns. | ||||||
| High‐dose versus low‐dose intranasal corticosteroids for chronic rhinosinusitis | ||||||
| Patient or population: chronic rhinosinusitis (all studies recruited patients with bilateral polyps) | ||||||
| Outcomes № of participants | Relative effect | Anticipated absolute effects* (95% CI) | Quality | What happens | ||
| Low‐dose intranasal corticosteroids | High‐dose intranasal corticosteroids | Difference | ||||
| Disease‐specific health‐related quality of life | Not measured | Impact unknown | ||||
| Disease severity ‐ overall symptoms, measured as average change from baseline at 4 months | ||||||
| All 4 EPOS domains | No information available | |||||
| 3 domains (nasal blockage, rhinorrhoea, loss of sense of smell) Range 0 to 3, lower score = less severe № of participants: 237 | — | The mean disease severity ‐ overall symptoms, measured as average change from baseline at 4 months (range 0 to 3) ‐ average symptom score (3 domains) without high‐dose was ‐0.66 points | — | MD 0.13 points lower (0.37 lower to 0.11 more) than low‐dose group | ⊕⊕⊝⊝ | The average score for 3 types of symptoms seems to be similar between the high‐dose and low‐dose groups. |
| (2 domains: nasal blockage, rhinorrhoea) № of participants: 441 | — | The mean disease severity ‐ overall symptoms, measured as average change from baseline at 4 months (range 0 to 3) ‐ average symptom score (2 domains) without high‐dose was ‐0.73 points | — | MD 0.19 points lower (0.36 lower to 0.02 lower) than low‐dose group | ⊕⊕⊝⊝ | The average score for 2 types of symptoms seems to be slightly lower for the high‐dose group. The clinical significance of this reduction is unclear. |
| Disease severity ‐ measured as average change from baseline at 4 months (range 0 to 3) | ||||||
|
№ of participants: 441 | — | The mean disease severity ‐ individual symptoms, measured as average change from baseline at 4 months (range 0 to 3) ‐ nasal blockage without high‐dose was ‐0.86 points | — | MD 0.24 points lower (0.39 lower to 0.08 lower) than low‐dose group | ⊕⊕⊝⊝ | The nasal blockage score seems to be slightly lower in the high‐dose group. The clinical significance of this reduction is unclear. |
|
№ of participants: 441 (2 RCTs) | — | The mean disease severity ‐ individual symptoms, measured as average change from baseline at 4 months (range 0 to 3) ‐ rhinorrhoea without high‐dose was ‐0.6 points | — | MD 0.15 points lower (0.33 lower to 0.03 higher) than low‐dose group | ⊕⊕⊝⊝ | The average score for rhinorrhoea seems to be similar between the high‐dose and low‐dose groups. |
|
№ of participants: 237 | — | The mean disease severity ‐ individual symptoms, measured as average change from baseline at 4 months (range 0 to 3) ‐ loss of sense of smell without high‐dose was ‐0.6 points | — | MD 0.06 points higher (0.2 lower to 0.32 higher) than low‐dose group | ⊕⊕⊝⊝ | The average score for loss of sense of smell seems to be very similar between the high‐dose and low‐dose groups. |
| Adverse effects: epistaxis № of participants: 637 | RR 2.06 | Study population | ⊕⊕⊕⊝ | The risk of epistaxis is likely to be higher in the higher‐dose groups. However, the studies included very minor nosebleeds, such as blood stains in the mucus, and most of these events are not likely to be severe. | ||
| 57 per 1000 | 118 per 1000 | 61 more per 1000 (11 more to 145 more) | ||||
| Moderate | ||||||
| 60 per 1000 | 124 per 1000 | 64 more per 1000 (12 more to 153 more) | ||||
| Adverse effects: local irritation № of participants: 542 | RR 0.97 | Study population | ⊕⊕⊝⊝ | The risk of local irritation seems to be similar between groups, but the overall risks are underestimated due to the way the data were reported. | ||
| 19 per 1000 | 18 per 1000 | 10 fewer per 1000 (13 fewer to 43 more) | ||||
| Moderate | ||||||
| 17 per 1000 | 17 per 1000 | 10 fewer per 1000 (13 fewer to 40 more) | ||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Scale validity, particularly discriminant validity (ability to distinguish the differences between groups), was unclear. There was a high risk of reporting bias. Studies tended to report enough information for meta‐analysis only for statistically significant results. One study, which had 101 participants, reported very similar values for both intervention arms for all disease scores but had no information related to SD. 2Small sample size ‐ evidence only from one or two relatively small studies. 3Only data from patients with bilateral nasal polyposis. We considered this to be indirectness of the evidence to patients without polyps but have not further downgraded the evidence. 4One of the studies had inadequate blinding ‐ a double dummy was not used to mask the twice daily (higher) versus once daily (lower) dose; the study had 101 participants. 5Sample size relatively small for a precise estimate of adverse events. We downgraded this outcome once, after taking into consideration the inadequate blinding in one of the studies and the relatively small sample size. 6Studies did not use consistent terminology/methods to report different types of local irritation. For analysis we only selected the most frequent types of local irritation from a list (to avoid double counting). This is a possible underestimation of overall event rates. The relatively low event rates and small sample size contributed to the large confidence intervals. | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Disease severity ‐ overall symptoms, measured as average change from baseline at 4 months (range 0 to 3) Show forest plot | 2 | Std. Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 1.1 Average symptom score (3 domains) | 1 | 237 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.14 [‐0.39, 0.12] |
| 1.2 Average symptom score (2 domains) | 2 | 441 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.21 [‐0.40, ‐0.03] |
| 2 Disease severity ‐ individual symptoms, measured as average change from baseline at 4 months (range 0 to 3) Show forest plot | 2 | Std. Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 2.1 Nasal blockage | 2 | 441 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.29 [‐0.47, ‐0.10] |
| 2.2 Rhinorrhoea | 2 | 441 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.15 [‐0.34, 0.03] |
| 2.3 Loss of sense of smell | 1 | 237 | Std. Mean Difference (IV, Random, 95% CI) | 0.06 [‐0.20, 0.31] |
| 3 Adverse effects: epistaxis Show forest plot | 4 | 637 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.06 [1.20, 3.54] |
| 4 Adverse effects: local irritation Show forest plot | 3 | 542 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.97 [0.28, 3.31] |
| 5 Nasal polyps size, measured as change from baseline (0 to 3 range scale) at 4 months Show forest plot | 1 | 237 | Mean Difference (IV, Fixed, 95% CI) | 0.19 [‐0.16, 0.54] |
| 6 Nasal polyps ‐ proportion with improvement at 12 weeks Show forest plot | 1 | 92 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.71 [0.91, 3.21] |
