[ Original Research Education, Research, and Quality Improvement ]

A Critical Review of the Quality of Cough

Clinical Practice Guidelines
Mei Jiang, PhD; Wei-jie Guan, PhD; Zhang-fu Fang, PhD; Yan-qing Xie, PhD; Jia-xing Xie, PhD; Hao Chen, MD;
Dang Wei, MD; Ke-fang Lai, MD; and Nan-shan Zhong, MD

BACKGROUND: Clinical practice guidelines (CPGs) have been developed to provide health-
care practitioners with the best possible evidence, but the quality of these CPGs varies greatly.
OBJECTIVE: The goal of this study was to systematically evaluate the quality of cough CPGs
and identify gaps limiting evidence-based practice.
METHODS: Systematic searches were conducted to identify cough CPGs in guideline data-
bases, developers’ Websites, and Medline. Four reviewers independently evaluated eligible
guidelines by using the Appraisal of Guidelines for Research and Evaluation II assessment
tool. Agreement among reviewers was measured by using the intraclass correlation coeffi-
cient. The number of recommendations, strength of recommendation, and levels of evidence
were determined.
RESULTS: Fifteen cough CPGs were identified. An overall high degree of agreement among
reviewers was observed (intraclass correlation coefficient, 0.82 [95% CI, 0.79-0.85]). The
quality ranged from good to acceptable in the scope and purpose (mean, 72%; range, 54%-
93%) and clarity and presentation (mean, 68%; range, 50%-90%) domains but not in
stakeholder involvement (mean, 36%; range, 18%-90%), rigor of development (mean, 36%;
range, 9%-93%), applicability (mean, 23%; range, 9%-83%), and editorial independence
domains (mean, 24%; range, 0-96%). Seven guidelines (46.7%) were considered “strongly
recommended” or “recommended with modifications” for clinical practice. More than 70% of
recommendations were based on nonrandomized studies (Level C, 30.4%) and expert
opinion (Level D, 41.3%).
CONCLUSIONS: The quality of cough CPGs is variable, and recommendations are largely
based on low-quality evidence. There is significant room for improvement to develop high-
quality guidelines, which urgently warrants first-class research to minimize the vital gaps in
the evidence for formulation of cough CPGs. CHEST 2016; 150(4):777-788

KEY WORDS: AGREE instrument; clinical practice guidelines; cough

FOR EDITORIAL COMMENT SEE PAGE 761

ABBREVIATIONS: AGREE = Appraisal for Research Guidelines Eval-
uation; CHEST = American College of Chest Physicians; CPG =
clinical practice guideline; NICE = National Institute for Health and
Clinical Excellence
AFFILIATIONS: From the State Key Laboratory of Respiratory Disease
(Drs Jiang, Guan, Fang, Y.-Q. Xie, J.-X. Xie, Lai, and Zhong), National
Clinical Research Center for Respiratory Disease, Guangzhou Institute
of Respiratory Diseases, First Affiliated Hospital of Guangzhou Med-
ical University, Guangzhou, China; The Second Clinical College (Dr
Chen), Nanjing University of Chinese Medicine, Nanjing, China; and
the Evidence-based Medicine Center (Dr Wei), School of Basic Medical
Sciences, Lanzhou University, Key Laboratory of Evidence Based
Medicine and Knowledge Translation of Gansu Province, Lanzhou,
China.

journal.publications.chestnet.org 777
Cough is one of the most common symptoms for which
patients seek medical care1 and constitutes a significant
health-care burden.2,3 Cough may be extremely
disruptive and has frequently been associated with
impaired quality of life,4,5 sleep disturbance,
absenteeism, social embarrassment, and other adverse
effects such as urinary incontinence.6,7 In the United
Kingdom, cough treatment resulted in approximately
$156 million in expenditures for a 52-week period
(survey ended on March 30, 2013),2 whereas in the
United States, the clinical need for nonspecific
antitussive drugs reached $3 billion annually and is
progressively increasing.8,9 Unfortunately, assessment
and management of cough remain the major challenge
for clinicians and vary significantly in practice.10
Cough guidelines drafted by local, national, and
international organizations have therefore been
developed to standardize clinical practice and improve
treatment outcomes.11 Ideally, evidence-based
guidelines are expected to combine current knowledge
that will aid clinical decision-making and identify the
major gaps between knowledge and treatment.2 The
usefulness of guidelines primarily depends on the
Materials and Methods
Identification of Guidelines
Systematic searches were performed with the Medline database
(through PubMed) combining the term “cough” and a filter to
identify guideline documents (Practice Guideline [pt] OR Guideline
[pt] OR guideline* [ti] OR consensus [ti]). The guideline database
and clearinghouses were searched by using the term “cough.”
Searches were limited to documents in English published up to
March 9, 2016. Results from the literature search were entered into a
bibliographic database, and duplicates were eliminated.
Two reviewers (M. J. and Y. X.) independently evaluated search results to
determine inclusion or exclusion of references, and extracted the general
characteristics of each guideline. Disagreements were resolved by
consensus or by consulting the third expert adjudicator (K. L.).
Selection of Guidelines
Documents were included that contained explicit clinical
recommendations on the diagnosis and management of cough
Drs Jiang and Guan contributed equally to the study.
FUNDING/SUPPORT: This work was supported by the National Nat-
ural Science Foundation of China [Grant No. 81402772].
CORRESPONDENCE TO: Ke-fang Lai, MD, State Key Laboratory of
Respiratory Disease, National Clinical Research Center for Respiratory
Disease, Guangzhou Institute of Respiratory Disease, First Affiliated
Hospital of Guangzhou Medical University, 151 Yanjiang Rd,
Guangzhou, Guangdong, China; e-mail: klai@163.com
Copyright Ó 2016 American College of Chest Physicians. Published by
Elsevier Inc. All rights reserved.
DOI: http://dx.doi.org/10.1016/j.chest.2016.04.028
778 Original Research
quality, rigorous methodology, and transparency of
development.12 It is important to determine whether
the recommendations are, indeed, based on high-
quality evidence.13,14 However, systemic appraisal of
existing cough guidelines is still lacking worldwide, and
the distribution of the levels of evidence underlying
the recommendations in cough guidelines has not
been delineated.
Notably, the quality of cough guidelines varies
considerably,11 calling for establishment of accepted
criteria for evaluating guidelines to improve their quality
and usefulness.15 The Appraisal of Guidelines for
Research and Evaluation II (AGREE II) is a reliable and
useful tool16 for assessment of guidelines.17,18 We
hypothesized that the quality of existing cough
guidelines could be systematically appraised by using the
AGREE II instrument, and we therefore thoroughly
reviewed guidelines on the diagnosis and management
of cough in peer-reviewed literature. The goal was to
assess the methodologic quality of the guidelines by
using the AGREE II instrument, identify gaps limiting
evidence-based practice, and highlight potential
opportunities for improvement.
guidelines published in peer-reviewed medical journals. If several
versions of documents were available, only the most up-to-date
version was selected. For every guideline ultimately included, we
thoroughly searched for accompanying technical and supporting
documents to better inform our assessments. The following
documents were excluded: systematic reviews, clinical trials,
editorials and letters, guidelines published in non-English languages
or published in other forms (ie, books, booklets, government
documents), and documents that were not available in full-text
format.
Evaluation of Guidelines
Eligible guidelines were independently evaluated by four reviewers
who were well trained in performing clinical practice guideline
(CPG) appraisals using the AGREE II instrument. Two reviewers
were respiratory physicians (W. G. and Y. X.), one was a public
health epidemiologist (M. J.), and the other was a guideline
methodologist (H. C.). AGREE II contains 23 items that are
categorized into six domains followed by two overall assessment
items. Each domain identified a unique dimension of the guideline’s
quality, and each item was assessed with a 7-point Likert score that
ranged from 1 (strongly disagree) to 7 (strongly agree). The
standardized score for the individual domain, which ranged from
0 to 100%, was calculated by using the following formula: (actual
score – minimal possible score)/(maximal possible score – minimal
possible score)
100%.19
Overall guideline evaluation reached consensus according to partial
item assessment and the global judgment by reviewers. The domains
rigor of development and applicability were assigned double weight.20
Each guideline was classified as: “strongly recommended” for overall
scores > 60%, “recommended with modifications” for scores between
30% and 60%, and “not recommended” for scores < 30%.
[ 150#4 CHEST OCTOBER 2016 ]
TABLE 1 ] A Composite Grading System for Ranking Recommendations in Cough Guidelines
Category Grade Definition
Quality of evidence A Randomized controlled trials without important limitations, or meta-analysis
B Randomized controlled trials with important limitations, or upgraded observational
studies
C Nonrandomized studies, cohort or case–control studies, case series
D Expert opinion
Strength of I Recommendation can apply to most patients in many circumstances
recommendation
II The best action may differ depending on circumstances or patients’ or societal values
UG Insufficient evidence on which to formulate a recommendation. The advantages and
disadvantages of the procedure/treatment are equivalent

UG ¼ ungraded.

Strength of Recommendation and Level of Evidence
Among nine evidence-based guidelines, four used the Grading of
Recommendations Assessment, Development and Evaluation
system21-24; four used the American College of Chest Physicians
(CHEST),2,25,26 Scottish Intercollegiate Guidelines Network,27 Société
Scientifique de Medicine Générale,28 and National Health and Medical
Research Council29 grading systems; and one (Clinical Expert
Guidelines for the Management of Cough in Lung Cancer)30 did not
mention which grading system was adopted. Despite the use of five
grading systems, these schemes were based on the same criteria and
comparable structures. Therefore, a composite grading system was
generated to represent all recommendations (Table 1). Only three
guidelines2,22,23 included the updated version, but the first version of
the two German cough guidelines22,23 were not published in English.
Because the latest version of the CHEST guideline (in 2014) has not
been completely updated, we compared the level of evidence and
strength of recommendations between the second version and the
latest version for the available contents. Evidence-based cough
guidelines were evaluated by comparing the strength of
recommendations within different types of recommendations
(Diagnostic Recommendation, Treatment Recommendation, and
Other Recommendations).
Statistical Analysis
The standardized score of each domain for individual CPGs was
calculated. The number of recommendations and the percent
distributions among quality of evidence and strength of
recommendation classes were determined. The c2 test or Fisher
exact test was used to compare the proportions of evidence or
recommendations.
Agreement among four reviewers was measured by using the intraclass
correlation coefficient (ICC) with 95% CIs. According to Landis and
Koch,31 the degree of agreement between 0.01 and 0.20 was deemed
minor, 0.21 to 0.40 was fair, 0.41 to 0.60 was moderate, 0.61 to 0.80
was substantial, and 0.81 to 1.00 was very good. A P value < .05
denoted statistical significance. All tests were two-sided. Statistical
analyses were conducted by using SPSS version 16 (IBM SPSS
Statistics, IBM Corporation).

Results All but two guidelines21,28 (n ¼ 13 [86.7%]) were

General Characteristics
There were 15 cough guidelines that met the inclusion
criteria published from 2004 through 2016 (Fig 1,
e-Table 1). Characteristics of eligible guidelines are listed
in Table 2. Of the 15 CPGs, five were developed by
international organizations2,32,33 or were from > 1
country.27,29 The remaining guidelines were from
Australia,21 Belgium,28 China,34 Germany,22,23 the
United Kingdom,30,35,36 Japan,37 and Korea.24 Four
guidelines (26.7%) targeted both adults and children. In
eight guidelines (53.3%), the target population was
exclusively adults, and three (20.0%) solely targeted
children. Most guidelines (n ¼ 12 [80.0%]) addressed
acute, subacute, and/or chronic cough, and the
remaining three focused on cough in palliative care,27
workplace-related cough,32 and cough in lung cancer.30
developed by medical societies.
Quality Assessment of Guidelines
Table 3 displays the AGREE II standardized domain scores
for each cough CPG and their overall recommendations.
The domain scope and purpose and the domain clarity and
presentation achieved the highest mean scores of
72% and 68% (range, 54%-93% and 50%-90%, respectively).
The mean score for the stakeholder involvement domain
was 36% (range, 18%-90%), with only one guideline scoring
> 60% and involving patient representatives during
development. The greatest range of scores was observed in
editorial independence (0-96%). Three guidelines (20.0%)
scored zero, and 13 guidelines (86.7%) scored < 50%. Rigor
of development and applicability yielded the lowest mean
scores of 36% and 23% (range, 9%-93% and 9%-83%). Not

journal.publications.chestnet.org 779
 Identification (6.7%) did not report the strength of recommendation,
556 references identified two guidelines21,28 (13.3%) did not report the level of
initially
evidence underpinning the recommendations, and one
guideline30 (6.7%) reported neither item.
81 references excluded
- Duplicated references (n = 80) Of 138 recommendations with the guidelines having the
- Not published in medical assigned levels of evidence, there was significant
journal (n = 1) variability regarding the levels of evidence, which
accounted for approximately 70% of recommendations
Screening

475 references screened based on Levels C and D evidence (30.4% and 41.3%,
by title and abstracts respectively) (Table 4).
Among 142 recommendations with guidelines having an
400 references excluded assigned strength of recommendations, 46.5% were
- Irrelevant references (n = 383) rated as strong (grade I), 39.4% as weak (grade II), and
- Non-English references (n = 17)
14.1% as ungraded. The majority of recommendations
were rated as strong (grade I) in the Australian and
Eligibility

75 references assessed German guidelines (scores of 61.3% and 59.5%,

by full text for eligibility
60 references excluded:
- Old version (n = 36)
- Sections of guidelines (n = 6)
- Narrative or systematic
reviews (n = 3)
- Interpretation of guidelines (n = 11)
- Letter or other (n = 4)
Included
respectively) but weak in other guidelines (Table 4).
Because the latest version of the CHEST guideline has
not been completely updated, we only compared the
level of evidence and strength of recommendation
between the second version and the latest version (2014)
for the available contents. Compared with the second
version of the CHEST guideline, the number of
recommendations of the published sections of the
CHEST 2014 cough guideline increased from 18 to 32

15 cough CPGs selected (77.8%); meanwhile, the number of Level C evidence

for evaluation
Figure 1 – Flowchart of cough guideline search and selection. CPGs ¼
clinical practice guidelines.
unexpectedly, four guidelines (26.7%) yielded the lowest
scores (# 10%) due to the failure in explicitly describing the
criteria for selecting evidence and formulating
recommendations. There was scant information regarding
potential organizational barriers, cost implications, and
tools for application except for the CHEST guideline.
Overall, the CHEST guideline scored higher on all
domains and was classified as strongly recommended for
clinical practice; six cough CPGs (40.0%) were
recommended with modifications; and eight (53.3%)
were not recommended. Overall, appraisers’ agreement
was very good (intraclass correlation coefficient, 0.82
[95% CI, 0.79-0.85]).
Level of Evidence and Strength of Recommendation
Among Evidence-based Cough Guidelines
Of the 15 guidelines, six (40.0%) were deemed not
evidence-based, whereas nine (60.0%) were evidence-
based, resulting in 176 recommendations. One guideline29
and expert opinion has dramatically increased (62.5%).
This change was partly because it applied a more
rigorous approach to scrutinize the evidence grade and
transparency of the grading; therefore, under the more
rigorous assessment of evidence, it would be more
difficult to achieve a higher grade.25
The most common type of recommendation was
Treatment Recommendations (63.6%), followed by
Diagnostic Recommendations (26.1%) and Other
Recommendations (10.3%). The Diagnostic
Recommendation categories had a predominance of
grade I recommendations (55.8%), whereas ungraded
recommendations were most commonly observed in the
Other Recommendations category (Fig 2).
Discussion
Principal Findings
Establishment of cough guidelines might be a complex
issue compared with that of other disease-specific
guidelines because cough is a global problem managed
by a variety of disciplines.2 In this study, the quality
of cough guidelines was highly heterogeneous among

780 Original Research [ 150#4 CHEST OCTOBER 2016 ]

TABLE 2 ] Characteristics of the Identified Guidelines on the Diagnosis and Management of Cough
Grading
Year of Issuing Country Adult/ Type of Development System
Title Publication Society Applied Version Children Cough Method Used
Overview of the 2014 CHEST International Updated Both Acute, EB CHEST
management of subacute
cough: CHEST and
Guideline and chronic
Expert Panel
Report2,a
Management of 2012 APMGBI Great Britain First Adult Cough in EB SIGN
chronic cough and palliative
in patients Ireland care
receiving
palliative care:
review of
evidence and
recommenda-
tions by a task
group of the
Association for
Palliative
Medicine of
Great Britain
and Ireland27
CICADA: Cough 2010 . Australia First Both Chronic EB GRADE
in Children and
Adults:
Diagnosis and
Assessment.
Australian
Cough
Guidelines
summary
statement21
Prolonged cough 2008 . Belgium First Children Chronic EB SSMG
in children: a
summary of
the Belgian
primary care
clinical
guideline28
Recommenda- 2006 BTS United First Adult Acute and CB None
tions for the Kingdom chronic
management
of cough in
adults35
Recommenda- 2008 BTS United First Children Acute and CB None
tions for the Kingdom chronic
assessment
and
management
of cough in
children36
The Chinese 2011 CSRD China First Adult Acute, CB None
national subacute
guidelines on and
diagnosis and chronic
management
of cough
(December
2010)34

(Continued)

journal.publications.chestnet.org 781
TABLE 2 ] (Continued)
Grading
Year of Issuing Country Adult/ Type of Development System
Title Publication Society Applied Version Children Cough Method Used
The Diagnosis 2014 DEGAM Germany Updated Adult Acute EB GRADE
and Treatment
of Acute Cough
in Adults23
EAACI Position 2014 EAACI International First Adult Workplace CB None
Paper on related
assessment of cough
cough in the
workplace32
The diagnosis and 2004 ERS International First Both Chronic CB None
management of
chronic cough33
Guidelines of the 2010 GRS Germany Updated Adult Acute and EB GRADE
German chronic
Respiratory
Society for
Diagnosis
and Treatment
of Adults
Suffering from
Acute or
Chronic
Cough22
The Japanese 2006 JRS Japan First Both Acute, CB None
Respiratory subacute
Society and
guidelines for chronic
management
of cough37
The Korean 2016 KATRD Korea First Adult Acute, EB GRADE
cough subacute
guideline: and
recommenda- chronic
tion and
summary
statement24
Cough in 2006 TSANZ Australia First Children Chronic EB NHMRC
children: and New
definitions and Zealand
clinical
evaluation29
Clinical expert 2010 UK task United First Adult Cough in EB Not
guidelines group Kingdom lung men-
for the cancer tioned
management of
cough in lung
cancer: report
of a UK task
group on
cough30

APMGBI ¼ Association for Palliative Medicine of Great Britain and Ireland; BTS ¼ British Thoracic Society; CB ¼ consensus-based; CHEST ¼ American
College of Chest Physicians; CSRD ¼ Chinese Society of Respiratory Diseases; DEGAM ¼ Deutsche Gesellschaft für Allgemeinmedizin und Familienmedizin
(the German College of General Practitioners and Family Physicians); EAACI ¼ European Academy of Allergy and Clinical Immunology; EB ¼ evidence-
based; ERS ¼ European Respiratory Society; GRADE ¼ Grading of Recommendations Assessment, Development and Evaluation; GRS ¼ German Respi-
ratory Society; JRS ¼ Japanese Respiratory Society; KATRD ¼ Korean Academy of Tuberculosis and Respiratory Diseases; NHMRC ¼ National Health and
Medical Research Council; SIGN ¼ Scottish Intercollegiate Guidelines Network; SSMG ¼ Société Scientifique de Medicine Générale; TSANZ ¼ Thoracic
Society of Australia and New Zealand.
a
The latest CHEST cough guideline has not been completely updated.

782 Original Research [ 150#4 CHEST OCTOBER 2016 ]

TABLE 3 ] AGREE II Domain Scores of Cough Guidelines and Overall Assessment
Scope and Stakeholder Rigor of Clarity and Editorial
Guideline Purpose Involvement Development Presentation Applicability Independence Overall Assessment
CHEST (Irwin et al, 93 90 93 90 83 96 Strongly
20142)a recommended
APMGBI (Wee et al, 54 25 36 54 10 10 Not
201227) recommended
Australia (Gibson 75 46 57 81 24 10 Recommended
et al, 201021) with
modifications
Belgium (Leconte 54 24 36 54 13 10 Not
et al, 200828) recommended
BTS (Morice et al, 81 42 45 82 38 71 Recommended
200635) with
modifications
BTS (Shields et al, 79 40 35 79 31 10 Recommended
200836) with
modifications
CSRD (Asthma 71 33 10 60 27 0 Not
Workgroup, recommended
CSRD, Chinese
Medical
Association,
201134)
DEGAM (Holzinger 60 18 48 69 13 38 Not
et al, 201423) recommended
EAACI (Moscato 72 26 9 58 18 10 Not
et al, 201432) recommended
ERS (Morice et al, 78 22 10 54 15 0 Not
200433) recommended
GRS (Kardos et al, 68 26 43 75 14 46 Recommended
201022) with
modifications
JRS (Kohno et al, 74 31 9 61 21 0 Not
200637) recommended
KATRD (Rhee et al, 65 43 47 74 16 13 Recommended
201624) with
modifications
TSANZ (Chang 81 32 34 78 16 42 Recommended
et al, 200629) with
modifications
UK task group 69 33 28 50 9 10 Not
(Molassiotis et al, recommended
201030)

AGREE ¼ Appraisal for Research Guidelines Evaluation. See Table 2 legend fort expansion of other abbreviations.
a
The latest ACCP cough guideline has not been completely updated.

different domains even within the same guideline. The
distribution of level of evidence and strength of
recommendations also varied significantly among
different categories of guidelines. More than 70% of
recommendations were only supported by Level C or D
evidence (nonrandomized studies or expert opinions,
respectively). Despite considerable improvement,
contemporary cough guidelines still lack a consolidated
evidence basis to offer recommendations for practice.
Additional research is needed to build the evidence base
to more robust levels, but the CHEST 2014 cough
guideline used a more rigorous approach to grade the
evidence, which might be associated with the
downgrading of much of the cough guidelines.25
Comparison With Other Studies
The quality of development and reporting of cough
guidelines seemed either comparable with, or superior

journal.publications.chestnet.org 783
TABLE 4 ] Distribution of the Strength of Recommendation and Level of Evidence Among Evidence-based Cough
Guidelinesa
Strength of Recommendation, No. (%) Level of Evidence, No. (%)
No. of
Guideline Recommendations I II UG A B C D
CHEST 32 12 (37.5) 8 (25.0) 12 (37.5) 0 6 (18.8) 14 (43.7) 12 (37.5)
(Irwin
et al,
20142)b
APMGBI 6 0 6 (100.0) 0 (0) 0 0 2 (33.3) 4 (66.7)
(Wee et al,
201227)
Australia 31 19 (61.3) 6 (19.3) 6 (19.3) . . . .
(Gibson
et al,
201021)
Belgium 7 0 7 (100.0) 0 . . . .
(Leconte
et al,
200828)
DEGAM 11 3 (27.3) 8 (72.7) 0 3 (27.3) 5 (45.4) 2 (18.2) 1 (9.1)
(Holzinger
et al,
201423)
GRS 37 22 (59.5) 13 (35.1) 2 (5.4) 2 (5.4) 11 (29.7) 7 (18.9) 17 (45.9)
(Kardos
et al,
201022)
KATRD 18 10 (55.6) 8 (44.4) 0 1 (5.5) 0 3 (16.7) 14 (77.8)
(Rhee
et al,
201624)
TSANZ 34 . . . 11 (32.3) 0 14 (41.2) 9 (26.5)
(Chang
et al,
200629)
Total, No. 176 66 (46.5)c 56 (39.4)c 20 (14.1)c 17 (12.3)d 22 (16.0)d 42 (30.4)d 57 (41.3)d
(%)

See Table 2 legend for expansion of abbreviations.

a
The guideline developed by UK task group (Molassiotis et al,30 2010) has not been listed because it failed to demonstrate the strength of recommendations
or the level of evidence in the documents.
b
Only the published sections of the latest ACCP cough guideline were counted.
c
Total number of recommendations excludes the guidelines that do not have any assigned strength of recommendations.
d
Total number of recommendations excludes the guidelines that do not have any assigned level of evidence.

to, other guidelines that focused on asthma,38 global AGREE II

diseases,39 and respiratory diseases in China20 (Fig 3).
Similar findings were found in terms of the scores of
individual domains among most guidelines. The 2014
CHEST cough guideline, which scored > 80% in all
domains, was rated as strongly recommended (Table 3).
Regarding the evidence basis of cough guidelines,
our findings agree with previous studies that many
guidelines were based largely on lower levels of
evidence14,40 or expert opinion,41 indicating that the lack
of high-quality evidence can be found not only in cough
guidelines but also in guidelines in other fields.
Improvements are needed in several domains.
Stakeholder involvement reflects how well guidelines
represent the views of its intended users, including the
patients. Implementation of CPGs requires the
contribution and expertise of a multidisciplinary
medical team, coupled with patient preferences. Patient’s
perspectives, expectations, and preferences of health care
have become increasingly crucial during guideline
development.42 However, except for the CHEST
guideline, no others have provided details regarding
involvement of patients or their representatives.

784 Original Research [ 150#4 CHEST OCTOBER 2016 ]

 Low performance was also found in the editorial
% of recommendations 70
60 56 Strong Weak UG None independence domain. Information related to potential
50 41 conflicts of interest was scarce or not mentioned.
40 34 34 Because conflicts of interest are the most common
30 23 23
21 19 18 18 source of bias44 and are frequently underreported,45
20 13
10
guideline developers should explicitly disclose the
0
0 conflicts of interest, including the rigorous vetting
Diagnosis Treatment Others
process and the transparent and available rules for
Figure 2 – Distribution of the strength of recommendation across review.46
different types of recommendations. The figures above the columns
indicate the items of recommendations. UG ¼ ungraded.
Level of Evidence

Rigor of development, the most critical domain,
markedly influences the confidence for guideline
implementation.38 Nonsystematic development readily
contributes to the low quality of guidelines.43 Four
guidelines (26.7%) did not describe the literature search
and selection methods, and they were ambiguous
regarding how evidence was appraised or
recommendations were formulated. The low score
might have resulted from the lack of methodologic
consultation38 or unfamiliarity with standards of
guideline development and poor reporting39 or poor
performance of external peer review and updating
processes.42
The score of applicability domain was disturbingly low,
suggesting that guideline developers have not paid
sufficient attention to potential barriers affecting
practical implementation of recommendations.15 Pilot
tests should be conducted to ensure feasibility prior to
publication.20 Guideline panels should address the
barriers and offer recommendations regarding who,
what, when, where, and how to provide as much
specificity as the evidence permits.
Our study
World guidelines
70
AGREE II Score (%)
Apart from the improvement in transparency and
methodologic rigor, cough guidelines should rest more
on the growing body of evidence. Notably, most
recommendations were based on low-quality evidence
(Levels C and D) (Table 4), which stemmed purely from
observational studies or expert consensus. This finding
constituted the major barrier for establishing national
cough guidelines because of the largely low-quality
evidence and has highlighted the gaps between clinical
practice evidence and current medical research.
Although there has been significant progress in the field
of cough, few guidelines have been updated. The CHEST
cough guideline, first published in 1998,47 was rewritten
with established methods in 200648 and updated in
2014.2,25,49-53
Although most recommendations of the 2014 CHEST
cough guideline were based on low-quality evidence
(Level C and expert opinion) compared with older
versions, it used a more rigorous approach to grade the
evidence, which might be associated with the
downgrading of much of the cough research in some
clinical areas.25 If there is insufficient or imperfect
evidence underpinning guideline recommendations,
well-conducted consensus statements can be clinically
Asthma guidelines
important, because they could still address important
Chinese respiratory guidelines
questions.25 Therefore, a hybrid model for providing
advice regarding the diagnosis and management of

60
cough has been applied to the development of the 2014
50 CHEST cough guideline, which combined an evidence-
40 based model and trustworthy consensus statements
30 based on a robust and transparent process. The 2014
20
CHEST cough guideline has increasingly become the
10
0 “living guideline,” which continually updates the
recommendations as new evidence, pharmacotherapies,
os d

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rp an

lv ld

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e

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lo ou

ab

or medical technologies become available.2

en rit
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es la

t
ve ig

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In e

E
o

ak

pl
Sc

St

The level of evidence of an identical recommendation

de
In

may vary considerably in different versions of

Figure 3 – Comparison of the quality of cough clinical practice guideline
with other guidelines. AGREE ¼ Appraisal for Research Guidelines guidelines. For instance, avoidance of environmental
Evaluation. tobacco smoke to prevent progression of bronchiectasis

journal.publications.chestnet.org 785
was classified as Level B evidence in the 1998 CHEST
guideline47 but became Level A evidence in the 2006
CHEST guideline.48 Similarly, use of antibiotics was
increasingly recommended for the management of
COPD exacerbations (from Level D to Level B).
This change suggests that an increased number of
well-conducted studies could have contributed to the
improved evidence base, translating into stronger
recommendations. However, recommendations might
vary among the guidelines developed by different
countries or regions, as exemplified by the use of
empirical antibiotics for management of acute bronchitis
(endorsed by the Chinese cough guideline34 but
discouraged by the 2006 CHEST guideline48). This
factor again warrants the integration of norms and
values of individual countries or regions, calling for
establishment of high-quality standards while balancing
patient needs, the level of evidence, and background of
different regions.
Recommendations to Improve Guideline Quality
Our findings call for meticulous quality standard re-
evaluation of existing guidelines and improvement of
quality for developing and reporting in practice. First,
apart from being familiar with guideline development
standards such as the AGREE II instrument,54
developers should apply these tools and delineate in the
guidelines whenever possible. Second, guidelines should
be stringently scrutinized for eligibility of quality
standards before release and subject to re-evaluation
periodically for necessary updates following publication.
Journal editors should set higher standards for peer
review; only the guidelines that met quality standards
could be considered for publication.
Third, guidelines development could also be constructed
on trustworthy consensus statements based on a robust
and transparent process when the evidence underpinning
recommendations is scant or imperfect.2,25,26 Fourth,
more attention should be paid to the controversy of
recommendation among countries or regions based on a
patient’s values and preferences, which have become
increasingly crucial during guideline development.
Furthermore, reinforcement of international
collaboration of guideline developers would help
minimize the overlapped efforts12,15 and resolve
controversy. Finally, guideline panels should address
barriers and offer recommendations regarding who,
what, when, where, and how to provide as much
specificity as the evidence permits.
786 Original Research
Limitations and Strengths
Our study has several limitations. Exclusion of CPGs
published in languages other than English, or in other
forms (ie, books, booklets, government documents),
might have resulted in underrepresentation of CPGs
from less developed countries. Second, the AGREE II
instrument focused on methods of guideline
development and the transparency of reporting but
could not assess potential impacts of recommendations
on patient outcomes.55,56 Furthermore, our study could
not establish causality between the poor performance
and the characteristics of cough CPGs. Matching current
guidelines to future guideline updates (in a cohort study)
would allow for better assessment of guideline quality
than did our cross-sectional assessment. Finally, although
our discussion delineated the CHEST cough guideline in
detail because it remains the only guideline that has an
updated version available for a head-to-head comparison,
most findings in our study regarding changes in the level
of evidence and strength of recommendation still apply
for other existing guidelines. We therefore believe that the
CHEST guideline should serve as the exemplification
rather than the sole standardized guideline for clinicians
and developers in real-world practice. Updates of other
guidelines in the future would provide more insights into
how the changes in a guideline’s quality would lead to
improved health care.
Nonetheless, our overall findings remained robust. Our
authors were from different backgrounds, consisting of
clinical experts and methodologists with extensive
experience in evaluating CPGs. Systematic literature
searches were conducted, and significant agreement
among reviewers was obtained, which improved the
reliability of our findings. Finally, different domains
have been appropriately weighted to derive overall
assessment and recommendation.
Conclusions
The quality of cough guidelines is highly variable.
High-quality guidelines are more likely to be formulated
by multidisciplinary teams. There is significant room for
improvement, especially in the rigor of development and
applicability domains. Cough guidelines should develop
recommendations with high-quality evidence while
minimizing bias from extrinsic sources with compelling
methodologic rigor and transparency. Whenever possible,
clinical practice guidelines should highlight the need for
additional research to fill the gaps within clinical care that
has the greatest impact on patient treatment outcomes.
[ 150#4 CHEST OCTOBER 2016 ]
Acknowledgments
Author contributions: M. J. had full access
to all of the data in the study and takes
responsibility for the integrity of the data and
the accuracy of the data analysis. M. J. and
W. G. contributed to the study concept, all
aspects of the study, and manuscript
preparation and revision; Y. X., J. X., Z. F.,
H. C., and W.D. contributed to the data
collection, data analysis, and interpretation;
and K. L. and N. Z. contributed to the study
design and critical review. All authors made
substantial contributions for important
intellectual and approved the final
manuscript.
Financial/nonfinancial disclosures: None
declared.
Role of sponsors: The sponsor had no role in
the design of the study, the collection and
analysis of the data, or the preparation of the
manuscript.
Additional information: The e-Table can be
found in the Supplemental Materials section
of the online article.
References
1. Marchant JM, Newcombe PA, Juniper EF,
Sheffield JK, Stathis SL, Chang AB. What
is the burden of chronic cough for
families? Chest. 2008;134(2):303-309.
2. Irwin RS, French CT, Lewis SZ,
Diekemper RL, Gold PM; for the CHEST
Expert Cough Panel. Overview of the
management of cough: CHEST Guideline
and Expert Panel Report. Chest.
2014;146(4):885-889.
3. Song WJ, Chang YS, Faruqi S, et al. The
global epidemiology of chronic cough in
adults: a systematic review and meta-
analysis. Eur Respir J. 2015;45(5):1479-1481.
4. Raj AA, Birring SS. Clinical assessment of
chronic cough severity. Pulm Pharmacol
Ther. 2007;20(4):334-337.
5. Chang AB, Robertson CF, Van
Asperen PP, et al. A multicenter study on
chronic cough in children: burden and
etiologies based on a standardized
management pathway. Chest. 2012;142(4):
943-950.
6. French CT, Fletcher KE, Irwin RS. Gender
differences in health-related quality of life
in patients complaining of chronic cough.
Chest. 2004;125(2):482-488.
7. Brignall K, Jayaraman B, Birring SS.
Quality of life and psychosocial aspects of
cough. Lung. 2008;186(suppl 1):S55-58.
8. Morice AH. Epidemiology of cough. Pulm
Pharmacol Ther. 2002;15(3):253-259.
9. Dicpinigaitis PV, Morice AH, Birring SS,
et al. Antitussive drugs—past, present, and
future. Pharmacol Rev. 2014;66(2):468-512.
10. Faruqi S, Murdoch RD, Allum F, et al. On
the definition of chronic cough and
current treatment pathways: an
international qualitative study. Cough.
2014;10:5.
11. Birring SS, Kavanagh J, Lai K, et al. Adult
and paediatric cough guidelines: Ready for
journal.publications.chestnet.org
an overhaul? Pulm Pharmacol Ther.
2015;35:137-144.
12. Grol R, Cluzeau FA, Burgers JS. Clinical
practice guidelines: towards better quality
guidelines and increased international
collaboration. Br J Cancer. 2003;89(suppl
1):S4-S8.
13. Isaac A, Saginur M, Hartling L, et al.
Quality of reporting and evidence in
American Academy of Pediatrics
guidelines. Pediatrics. 2013;131(4):
732-738.
14. Khan AR, Khan S, Zimmerman V, et al.
Quality and strength of evidence of the
Infectious Diseases Society of America
clinical practice guidelines. Clin Infect Dis.
2010;51(10):1147-1156.
15. Lytras T, Bonovas S, Chronis C, et al.
Occupational asthma guidelines: a
systematic quality appraisal using the
AGREE II instrument. Occup Environ
Med. 2014;71(2):81-86.
16. MacDermid JC, Brooks D, Solway S, et al.
Reliability and validity of the AGREE
instrument used by physical therapists in
assessment of clinical practice guidelines.
BMC Health Serv Res. 2005;5(1):18.
17. Brouwers MC, Kho ME, Browman GP,
et al. AGREE II: advancing guideline
development, reporting and evaluation in
health care. CMAJ. 2010;182(18):E839-E842.
18. Burls A. AGREE II-improving the quality
of clinical care. Lancet. 2010;376(9747):
1128-1129.
19. AGREE Next Steps Consortium. The
AGREE II instrument. Minervation
Website. www.agreetrust.org. Accessed
March 3, 2016.
20. Jiang M, Liao LY, Liu XQ, et al. The
quality assessment of clinical practice
guidelines for respiratory diseases in
China: a systematic appraisal. Chest.
2015;148(3):759-766.
21. Gibson PG, Chang AB, Glasgow NJ, et al.
CICADA: Cough in Children and Adults:
Diagnosis and Assessment. Australian
cough guidelines summary statement.
Med J Aust. 2010;192(5):265-271.
22. Kardos P, Berck H, Fuchs KH, et al.
Guidelines of the German Respiratory
Society for diagnosis and treatment of
adults suffering from acute or chronic
cough. Pneumologie. 2010;64(11):701-711.
23. Holzinger F, Beck S, Dini L, et al. The
diagnosis and treatment of acute cough in
adults. Dtsch Arztebl Int. 2014;111(20):
356-363.
24. Rhee CK, Jung JY, Lee SW, et al. The Korean
Cough Guideline: recommendation and
summary statement. Tuberc Respir Dis
(Seoul). 2016;79(1):14-21.
25. Lewis SZ, Diekemper RL, French CT,
Gold PM, Irwin RS; for the CHEST Expert
Cough Panel. Methodologies for the
development of the management of
cough: CHEST guideline and expert panel
report. Chest. 2014;146(5):1395-1402.
26. Lewis SZ, Diekemper R, Ornelas J,
Casey KR. Methodologies for the
development of CHEST guidelines and
expert panel reports. Chest. 2014;146(1):
182-192.
27. Wee B, Browning J, Adams A, et al.
Management of chronic cough in patients
receiving palliative care: review of
evidence and recommendations by a task
group of the Association for Palliative
Medicine of Great Britain and Ireland.
Palliat Med. 2012;26(6):780-787.
28. Leconte S, Paulus D, Degryse J. Prolonged
cough in children: a summary of the
Belgian primary care clinical guideline.
Prim Care Respir J. 2008;17(4):206-211.
29. Chang AB, Landau LI, Van Asperen PP,
et al. Cough in children: definitions and
clinical evaluation. Med J Aust.
2006;184(8):398-403.
30. Molassiotis A, Smith JA, Bennett MI, et al.
Clinical expert guidelines for the
management of cough in lung cancer:
report of a UK task group on cough.
Cough. 2010;6:9.
31. Landis RJ, Koch GG. The measurement of
observer agreement for categorical data.
Biometrics. 1977;33(1):159-174.
32. Moscato G, Pala G, Cullinan P, et al.
EAACI position paper on assessment of
cough in the workplace. Allergy.
2014;69(3):292-304.
33. Morice AH, Fontana GA, Sovijarvi AR,
et al. The diagnosis and management of
chronic cough. Eur Respir J. 2004;24(3):
481-492.
34. Asthma Workgroup, Chinese Society of
Respiratory Diseases (CSRD), Chinese
Medical Association. The Chinese
national guidelines on diagnosis and
management of cough (December 2010).
Chin Med J (Engl). 2011;124(20):
3207-3219.
35. Morice AH, McGarvey L, Pavord I, et al.
Recommendations for the management of
cough in adults. Thorax. 2006;61(suppl 1):
i1-i24.
36. Shields MD, Bush A, Everard ML, et al.
BTS guidelines: recommendations for the
assessment and management of cough in
children. Thorax. 2008;63 Suppl 3:
iii1-iii15.
37. Committee for the Japanese Respiratory
Society Guidelines for Management of
Cough; Kohno S, Ishida T, et al. The
Japanese Respiratory Society guidelines
for management of cough. Respirology.
2006;11(suppl 4):S135-S186.
38. Acuna-Izcaray A, Sanchez-Angarita E,
Plaza V, et al. Quality assessment of
asthma clinical practice guidelines: a
systematic appraisal. Chest. 2013;144(2):
390-397.
39. Alonso-Coello P, Irfan A, Sola I, et al. The
quality of clinical practice guidelines over
the last two decades: a systematic review
of guideline appraisal studies. Qual Saf
Health Care. 2010;19(6):e58.
40. Tricoci P, Allen JM, Kramer JM, et al.
Scientific evidence underlying the ACC/
AHA clinical practice guidelines. JAMA.
2009;301(8):831-841.
41. Harpole LH, Kelley MJ, Schreiber G,
Toloza EM, Kolimaga J, McCrory DC.
787
 Assessment of the scope and quality of
clinical practice guidelines in lung cancer.
Chest. 2003;123(suppl 1):7S-20S.
42. Gallardo CR, Rigau D, Irfan A, et al.
Quality of tuberculosis guidelines: urgent
need for improvement. Int J Tuberc Lung
Dis. 2010;14(8):1045-1051.
43. Burgers JS, Cluzeau FA, Hanna SE, et al.
Characteristics of high-quality guidelines:
evaluation of 86 clinical guidelines
developed in ten European countries and
Canada. Int J Technol Assess Health Care.
2003;19(1):148-157.
44. Detsky AS. Sources of bias for authors of
clinical practice guidelines. CMAJ.
2006;175(9):1033-1035.
45. Neuman J, Korenstein D, Ross JS, et al.
Prevalence of financial conflicts of interest
among panel members producing clinical
practice guidelines in Canada and United
States: cross sectional study. BMJ.
2011;343:d5621.
46. Norris SL, Holmer HK, Ogden LA, et al.
Conflict of interest in clinical practice
guideline development: a systematic
review. PLoS One. 2011;6(10):e25153.
47. Irwin RS, Boulet LP, Cloutier MM, et al.
Managing cough as a defense mechanism
and as a symptom. A consensus panel
788 Original Research
report of the American College of Chest
Physicians. Chest. 1998;114(suppl
managing 2):133S-181S.
48. Irwin RS, Baumann MH, Bolser DC, et al;
for the American College of Chest
Physicans. Diagnosis and management of
cough executive summary: ACCP
evidence-based clinical practice guidelines.
Chest. 2006;129(suppl 1):1S-23S.
49. Canning BJ, Chang AB, Bolser DC,
Smith JA, Mazzone SB, McGarvey L; for
the CHEST Expert Cough Panel. Anatomy
and neurophysiology of cough: CHEST
Guideline and Expert Panel report. Chest.
2014;146(6):1633-1648.
50. Boulet LP, Coeytaux RR, McCrory DC,
et al; for the CHEST Expert Cough Panel.
Tools for assessing outcomes in studies of
chronic cough: CHEST guideline and
expert panel report. Chest. 2015;147(3):
804-814.
51. French CT, Diekemper RL, Irwin RS;
for the CHEST Expert Cough Panel.
Assessment of intervention fidelity
and recommendations for researchers
conducting studies on the diagnosis
and treatment of chronic cough in
the adult: CHEST Guideline and Expert
Panel Report. Chest. 2015;148(1):
32-54.
52. Vertigan AE, Murad MH, Pringsheim T,
et al; for the CHEST Expert Cough Panel.
Somatic cough syndrome (previously
referred to as psychogenic cough) and tic
cough (previously referred to as habit
cough) in adults and children: CHEST
Guideline and Expert Panel Report. Chest.
2015;148(1):24-31.
53. Gibson P, Wang G, McGarvey L,
Vertigan AE, Altman KW, Birring SS; for
the CHEST Expert Cough Panel.
Treatment of unexplained chronic cough:
CHEST Guideline and Expert Panel
Report. Chest. 2016;149(1):27-44.
54. Shaneyfelt TM, Mayo-Smith MF,
Rothwangl J. Are guidelines following
guidelines? The methodological quality of
clinical practice guidelines in the peer-
reviewed medical literature. JAMA.
1999;281(20):1900-1905.
55. Vlayen J, Aertgeerts B, Hannes K, et al.
A systematic review of appraisal tools for
clinical practice guidelines: multiple
similarities and one common deficit. Int J
Qual Health Care. 2005;17(3):235-242.
56. Watine J, Friedberg B, Nagy E, et al.
Conflict between guideline methodologic
quality and recommendation validity: a
potential problem for practitioners. Clin
Chem. 2006;52(1):65-72.
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