An Osteopathic Modular Approach to Asthma: A Narrative Review

Abstract

Asthma is among of the first ailments documented in the existing academic literature as being successfully managed with osteopathic manipulative treatment (OMT) techniques. Time-efficient and well-tolerated OMT techniques have been gradually added to the literature to manage this increasingly prevalent disease. In this narrative review, the authors discuss previously-published literature describing the history, diagnosis, and management of asthma related to osteopathic principles and practices and OMT application. They also present current and newly-approved medical managements, including biologics and inhaled corticosteroids. This article also includes supplemental videos showcasing OMT techniques for asthma management, which were developed by the authors based on recommendations indicated in the literature.

Full text

An Osteopathic Modular Approach to Asthma:
A Narrative Review
Jason Schend, DO; Marija Rowane, OMS III; Neha Sanan, DO;
Sir Robert Hostoffer, Jr., DO, LhD, MSMEd
From the University Hospitals
(UH) Pediatric & Adult Allergy/
Immunology Fellowship
Program, Department of
Pulmonary Critical Care at
University Hospitals Cleveland
Medical Center in Cleveland,
Ohio (Drs. Schend, Sanan,
and Hostoffer); and the Ohio
University Heritage College of
Osteopathic Medicine in
Athens, Ohio (Student
Dr Rowane).
Disclaimer: Dr Hostoffer is the
American Osteopathic
Association Board of Trustees
representative on the JAOA’s
Editorial Board.
Financial Disclosures: None
reported.
Support: None reported.
Address correspondence to
Marija Rowane, OMS III,
Allergy/ Immunology
Associates, Inc.,
5915 Landerbrook Drive,
Suite 110, Mayfield Heights,
Ohio 44124-4034.
Email:
mr388917@ohio.edu
Submitted
August 7, 2019;
revision received
December 16, 2019;
accepted
February 10, 2020.
Asthma is among of the first ailments documented in the existing academic
literature as being successfully managed with osteopathic manipulative treat-
ment (OMT) techniques. Time-efficient and well-tolerated OMT techniques
have been gradually added to the literature to manage this increasingly
prevalent disease. In this narrative review, the authors discuss previously-
published literature describing the history, diagnosis, and management of
asthma related to osteopathic principles and practices and OMT application.
They also present current and newly-approved medical managements,
including biologics and inhaled corticosteroids. This article also includes
supplemental videos showcasing OMT techniques for asthma management,
which were developed by the authors based on recommendations indicated
in the literature.
J Am Osteopath Assoc. 2020;120(11):774-782. Published online September 22, 2020.
doi:10.7556/jaoa.2020.121
Keywords: asthma, bronchial asthma, bronchitis, chronic lung disease, COPD, OMT
Asthma and its management have been recognized for millennia and recorded in
both medical and nonmedical literature. Since the oldest historical reference of
the “noisy”and “troubled”breathing of patients with asthma was described by
China’s Emporer Huang Ti (2698-2598 BC)
1
and Hippocrates’description of άσθμα (“to
exhale with an open mouth, to pant”),
2
our understanding of asthma has evolved to the
molecular mechanisms and advanced management of today, far beyond the initial inhal-
ation apparatuses described in Ebers Papyrus.
3
Contemporary practice includes pharma-
cologic therapies like inhaled corticosteroids (ICS) and biological agents, specific to the
various asthma phenotypes: early-onset allergic, late-onset eosinophilic,
exercise-induced, obesity-related, and neutrophilic asthma (Table 1).
4-5
The Global
Initiative for Asthma (GINA) has recommended personalized management to control
asthma symptoms and minimize future exacerbation risk, beginning with low-dose ICSs
and short-acting beta-agonists (SABAs) as needed (Table 2).
6
Biological therapy has
been a topic of increasingly-frequent research and is in demand for decreasing severe
airway inflammation during asthma exacerbations (Table 3).
6-18
Osteopathic treatment for asthma began in the 1870s and has targeted 3 areas: addres-
sing somatic dysfunction of thoracic spine and ribs, improving diaphragmatic function,
and balancing sympathetic and parasympathetic dysregulation.
19-24
Patients with asthma
have multiple systems involved in the inherent pathophysiology of their disease: biomech-
anical, metabolic, respiratory/circulatory, musculoskeletal, and behavioral. Early
REVIEW
774 The Journal of the American Osteopathic Association November 2020 |Vol 120 |No. 11

20
th
-century discussions by Moore
21
and Oium,
22
a
1993 editorial by Allen and D’Alonzo,
23
a 1996 clinical
practice guide by Paul and Buser,
24
1999 literature
reviews by W.A. and M.P. Rowane
19
and Jackson and
Steele,
20
a 2004 review by Salamon,
25
and a 2013 sys-
temic review of randomized control trials (RCTs) by
Piosadski et al
26
are among the limited osteopathic lit-
erature describing the pathogenesis and osteopathic treat-
ment of asthma.
27-30
Other studies have provided
evidence of the benefit of osteopathic manipulative treat-
ment (OMT) through pilot studies
31-32
and a pediatric
randomized clinical trials (RCTs),
26,28,30
as well as evi-
dence regarding other nonpharmacologic therapies,
such as acupuncture and chiropractic
manipulation,
30,33-35
in asthma management. No animal
models, nor any expansive clinical studies or RCTs,
exist in the literature to further support recommendations
for these adjunctive therapies. Here, we present an
updated review of asthma, its pharmacologic treatments,
and the most common and effective OMT techniques for
managing this chronic lung disease.
Literature Search Methods
We performed a targeted search through osteopathic
medical libraries and various databases, including the
Museum of Osteopathic Medicine and International
Center for Osteopathic History (ICOH) at A.T. Still
University, PubMed, Osteopathic Medical Digital
Repository (OSTMED. DR), Lippincott Williams and
Wilkins Health Library/Osteopathic Health Library,
Ovid, Cochrane Library, and Google Scholar. Search
terms included osteopathic manipulative treatment,
OMT, osteopathic manipulative medicine, OMM, osteo-
pathic principles and practices, OPP, asthma,bron-
chial asthma, chronic lung disease, COPD, and
bronchitis. Our searches were conducted without limi-
tation on publication dates. A total of 32 manuscripts
published between 1899 and 2019 contained informa-
tion about osteopathic physicians’approaches to
asthma.
24-30,33-63
Several contained information about
current and newly approved medical treatments, includ-
ing biologics and inhalers (Table 2,Table 3).
60-62
We
reviewed each publication for its methodology, size,
Table 1.
Asthma Phenotypes and Clinical Characteristics
Phenotypes
Natural history and clinical
characteristics
Pathology and
biomarkers Therapies
Early-onset allergic Early onset; mild-to-severe symptoms;
frequently associated with atopy
Elevated Total/Specific
IgE; Th2 cytokines;
thickened SBM
Monoclonal antibody to IgE,
Th2-targeted CS
Late-onset
eosinophilic
Adult onset; often severe symptoms;
increased eosinophils in sputum; less
allergic; includes AERD
CS-refractory
eosinophilia; IL-5
Monoclonal antibodies to IL-5/
IL-5R, IL-4R and cysteinyl
leukotriene modifiers
Exercise-induced Intermittent with exercise; mild
symptoms
Mast-cell activation; Th2
cytokines; cysteinyl
leukotrienes
Cysteinyl leukotriene modifiers,
beta agonists, antibody to IL-9
Obesity-related Adult onset; females; increased OCS
use; nonatopic
Lack of Th2 biomarkers;
oxidative stress
Weight loss, antioxidants,
hormonal therapy
Neutrophilic Low FEV
1
; significant air trapping;
frequent OCS use
Sputum neutrophilia;
Th17 pathways; IL-8
Macrolide antibiotics
Abbreviations: AERD, aspirin-exacerbated respiratory disease; CS, corticosteroids; IL, interleukin; IgE, immunoglobulin E; FEV
1
, forced
expiratory volume in 1 second; OCS, oral corticosteroids; SBM, subepithelial basement membrane.
Adapted from Wenzel 2012
4
and Tabatabaian 2019.
5
REVIEW
The Journal of the American Osteopathic Association November 2020 |Vol 120 |No. 11 775

Table 2B.
Differentiation of Inhaled Corticosteriods According to Potency*
Low-dose mcg Medium-dose mcg High-dose mcg
Beclomethasone
dipropionate (HFA)
Budesonide (DPI)
Ciclesonide (HFA)
Fluticasone furoate (DPI)
Fluticasone propionate
(DPI or HFA)
Mometasone furoate
Triamcinolone acetonide
100–200
200–400
80-160
100
100-250
110-220
400-1000
Beclomethasone
dipropionate (HFA)
Budesonide(DPI)
Ciclesonide (HFA)
Fluticasone propionate
(DPI or HFA)
Mometasone furoate
Triamcinolone acetonide
>200-400
>400-800
>160-320
>250-500
>220-440
>1000-2000
Beclomethasone
dipropionate (HFA)
Budesonide (DPI)
Ciclesonide (HFA)
Fluticasone furoate (DPI)
Fluticasone propionate
(DPI or HFA)
Mometasone furoate
Triamcinolone acetonide
>400
>800
>320
200
>500
>440
>2000
Abbreviations: DPI, dry powder inhaler; HFA, hydrofluoroalkane propellant.
*Refer to Table 2A for an outline of preferred controllers and relievers.
Adapted from Tabatabaian 2019
5
and Global Initiative for Asthma (GINA) 2019.
6
Table 2A.
Personalized Asthma Step Management for Adults and Adolescents (≥12 years old) to Control
Symptoms and Minimize Future Exacerbation Risk: Preferred Controllers and Relievers*
Step Preferred controller Other controller Preferred reliever
Other
reliever
options
1As-needed low-dose ICS-formoterol
a
Low-dose ICS with
SABA
b
As-needed low-dose
ICS-formoterol
a
As-needed
SABA
2Daily low-dose ICS, or as-needed low
dose ICS-formoterol
a
LTRA, low-dose ICS
with SABA
b
……
3Low-dose ICS-LABA Medium-dose ICS,
or low-dose ICS
+LTRA
d
As-needed low dose
ICS-formoterol for patient
prescribed maintenance and
reliever therapy
c
…
4Medium-dose ICS-LABA High-dose ICS, add
tiotropium or LTRA
d
……
5High-dose ICS-LABA, refer for
phenotypic assessment and/or add
therapy, e.g. tiotropium, anti-IgE,
anti-IL5/5R, anti-IL4R
Low-dose OCS
e
……
a
off-label, data only with budesonide-formoterol (bud-form);
b
off-label, separate or combination ICS and SABA inhalers;
c
low-dose ICS-form is
the reliever for patients prescribed bud-form or beclomethasone-diproprionate form maintenance and reliever therapy;
d
consider adding
house dust mites sublingual immunotherapy for sensitized patients with allergic rhinitis and FEV1 >70% predicted;
e
consider side effects
DPI.
*Refer to Table 2B for specific inhaled corticosteroid potencies and dosages.
Abbreviations: DPI, dry powder inhaler; ICS, inhaled corticosteroid; IgE, immunoglobulin E; IL, interleukin; LTRA, leukotriene-receptor
antagonist; LABA, long-acting β2-agonist; OCS, oral corticosteroids; SABA, Short-acting β2-agonist.
Adapted from Tabatabaian 2019
5
and Global Initiative for Asthma (GINA) 2019.
6
REVIEW
776 The Journal of the American Osteopathic Association November 2020 |Vol 120 |No. 11

scope, and relevance to the management of asthma for
the practicing clinician. The results of these studies are
discussed below by topic.
Biomechanical Mechanism of Treatment
Somatic dysfunction leading to bronchospasm, via
aberrant viscerosomatic sympathetic tone, has been
associated with bilateral and ipsilateral T2-T7 thoracic
segments.
47-49
Allen and Alonzo
23
documented
common dysfunctions recognized in acute asthma,
including “lesions”in the “second to fourth thoracic
vertebra,”elevation of the “fourth rib of the right,”and
a“lesion of the third cervical vertebrae with rotation to
the left.”Asthma symptoms, including bronchospasm
and increased mucus production, have also been attrib-
uted to elevated parasympathetic tone.
52
Rib and spinal
segmental dysfunction can lead to a reduction in
optimal ventilation.
34
Musculature that supports these
bony structures can become hypertonic or even fatigued
to the point of failure. Direct and indirect OMT techni-
ques can help to maximize chest wall excursion in both
inhalation and exhalation.
24
Common techniques to manage acute asthma exacer-
bations include various combinations of rib raising,
myofascial release (MFR), balanced ligamentous
tension (BLT), high velocity-low amplitude (HVLA),
and thoracic pump.
33,52
Fatigued hypertonic accessory
muscle groups include the cervical strap and intercostal
muscles. BLT and the other OMT techniques may be
performed several times, as needed, when the patient
remains dyspneic and struggles to breathe.
51
Guiney
et al
28
conducted an RCT using rib raising, muscle
energy, and myofascial release in an OMT sequence
that resulted in notable improvements (25%-70%) in
patients’peak expiratory flow (PEF) rates in 90 female
pediatric patients’peak expiratory flow rates and, ultim-
ately, chest wall motion.
34
Direct and indirect inhibition of parasympathetic tone
has been described by osteopathic physicians for over a
century as an asthma management.
26,34,53,54
Addressing
Table 3.
Biologics Targeting T2-high Asthma
Therapies Mechanism of action Potential biomarkers Effect
Omalizumab Blocks IgE interaction with
FcεRI
Elevated IgE, FeNO, blood
eosinophils (>300 cells/μL)
Decrease
asthma
exacerbations
…
Mepolizumab IL-5 antagonist Peripheral eosinophil count
>150 cells/μL or 300 cells/μL
Decrease
asthma
exacerbations
Improvement in
pre-post
bronchodilator FEV
1
Reslizumab IL-5 antagonist Peripheral eosinophil count
>400 cells/μL
Decrease
asthma
exacerbations
Improvement in
FEV
1
Benralizumab IL-5 receptor; α-antagonists
targeting both eosinophils and
basophils
Elevated peripheral blood
eosinophil count
Decrease
asthma
exacerbations
…
Dupilumab Inhibits IL-13 and IL-4 by
targeting IL-4-αreceptor
(common receptor domain for
both cytokines)
Improvements in all patient;
better response if peripheral
eosinophil count >300 cells/μL
or sputum >3%
Decrease
asthma
exacerbations
Improvement in
FEV
1
Abbreviations: FcεRI, high affinity receptor for the fragmented crystallizable region of immunoglobulin E; FeNO, fractional exhaled nitric oxide
FEV
1
, forced expiratory volume in 1 second; IgE, immunoglobulin E; IL, interleukin.
Adapted from information provided in Tabatabaian,
5
Hanania et al,
7
Humbert et al,
8
Pavord et al,
9
Haldar et al,
10
Flood-Page et al,
11
Ortega
et al,
12
Corren et al,
13
Laviolette et al,
14
Nowak et al,
15
Wenzel et al,
16
Castro et al,
17
Busse et al
18
REVIEW
The Journal of the American Osteopathic Association November 2020 |Vol 120 |No. 11 777

the occipitoatlantal (OA) region via decompression, the
upper cervical spine via MFR and strain-counterstrain,
and the vagus nerve via direct inhibition can lessen
bronchoconstriction present in the asthmatic airway
(Supplemental Video 1 and Video 2).
26
Decreased
mucus production may require more time to resolve and
may therefore necessitate repeated treatments.
Respiratory/Circulatory Mechanism
of Treatment
The pump action of the abdominal diaphragm is not
only vital for gas exchange, but it also has an integral
role in lymphatic drainage and the low-pressure vascu-
lar circulatory loop in the lungs.
63
Although OMT did
not change vital capacity or residual volume in prelim-
inary studies reported by Allen and D’Alonzo,
23
improved work capacity, arterial carbon dioxide
tension, oxygen saturation, total lung capacity, and
residual volume, as well as reduced dyspnea and fewer
upper respiratory tract infections, have been demon-
strated from OMT elsewhere. Creasy et al
51
demon-
strated that diaphragmatic movement is a crucial
element in maintaining lymph and vascular flow in the
thoracic and abdominal spaces. In the supplemental
videos accompanying this manuscript, we demonstrate
thoracic pump and diaphragm doming techniques for
addressing these mechanisms.
OMT techniques are helpful as an adjunct therapy for
asthma exacerbations to improve mechanical function-
ing of the thoracic cage and balance the autonomic
nervous system.
48
Guiney et al,
28
Bockenhauer et al,
27
and Allen and Kelso
42
demonstrated direct effect of
OMT on mechanical restrictions and respiratory excur-
sion in patients with respiratory disease. Although
Guiney et al
28
improved peak expiratory flow rates
after OMT application (7-9 L/min, 22% increase),
forced expiratory volume in 1 second (FEV
1
), and flow-
controlled ventilation (FVC) would provide a more
accurate assessment of respiratory function. Regardless,
OMT intervention has been beneficial for asthma man-
agement by decreasing anxiety resulting from respira-
tory distress and improving chest wall function.
48
Metabolic Mechanism of Management
Strides have been made in the last several years in
asthma management. Inhaled corticosteroids, long-
acting beta agonists, anticholinergics (including long-
acting formulations now approved for asthma), arachi-
donic acid pathway inhibitors, and monoclonal anti-
bodies—collectively referred to as “biologics”—are
the latest evolutions in asthma treatment.
60-62
Targeted
therapies using biologics to alter pathologic pathways
are now approved for patients with moderate-to-severe,
persistent asthma.
60-62
(Table 3)
Classifying asthma phenotypes is a burgeoning
approach to determine which of the 5 biologics on the
market to prescribe for asthma management.
62
Omalizumab was the first FDA-approved monoclonal
antibody for asthma treatment.
7-8,62
Its mechanism of
action is binding unbound immunoglobulin E (IgE) in
tissues and circulation.
7-8,62
IgE is ligated to omalizu-
mab, blocked from receptor binding, and prevented
from receptor cross-linking, subsequently leading to
granulocyte degranulation.
7-8,62
Mepolizumab is an interleukin (IL)-5 antagonist that
has potent antieosinophilic and inflammatory action in
the lungs.
9-12,62
Elevated eosinophil levels are
common in patients with moderate-to-severe persistent
asthma.
8-9,62
Reslizumab is another IL-5 antagonist,
available only as an infusion and dosed by weight;
thus, it is useful for patients with higher BMIs.
13,62
Benralizumab is an IL-5 receptor antagonist that not
only blocks the effects of eosinophils but also reduces
their number and longevity.
14-15,62
Dupilumab is an IL-4 receptor α-subunit antagonist
that works to mitigate the effects of potent inflamma-
tory ILs, including IL-4 and IL-13.
16-17,62
The advent
of biologics is viewed as a major “game-changer”for
chronic diseases across many fields.
Neurologic Mechanism of Treatment
In the early 20
th
century, Coffman argued against the
popular belief that asthma was not a primary neurosis
manifested solely by psychological perturbations.
52
He
stated that the neurologic component of asthma was an
REVIEW
778 The Journal of the American Osteopathic Association November 2020 |Vol 120 |No. 11

integral part of the disease pathophysiology, but was
not “all in the head”of the patient.
52
He reasoned that
any neurosis was secondary “to a disturbance of the
muscles of the bronchi, producing dyspnae,”leading
to anxiety associated with shortness of breath.
52
Henley et al emphasized OMT to address the adversar-
ial roles of the sympathetic chain (T1-T6) and parasym-
pathetics (vagus nerve) that innervate bronchial smooth
muscles.
53
Management that helps normalize sympa-
thetic tone by addressing somatic dysfunctions can be
used.
19,49
Rib raising and thoracic HVLA are
2 common OMT techniques that may occupy a few
minutes at the end of the physical examination
(Supplemental Videos 1 and 2). Gentle craniosacral
techniques are additionally proposed to address
common conditions, as well as asthma symptoms.
42
Osteopathic interventions that improve thoracic
mobility favorably affect the regulatory mechanisms of
the autonomic nervous system.
27
Parasympathetic
innervation sets the tone in the bronchial smooth
muscles. Increased parasympathetic expression can
lead to bronchoconstriction. Parasympathetic signaling
also increases secretory function in many tissues that
may instigate mucus hypersecretion in the lungs.
Pathologic deviations in parasympathetic tone have
been associated with reduced response to adrenergic
agonists and exaggerated responses to cholinergic med-
ications that lead to increased parasympathetic tone.
64
Oium
22
substantiated the application of OA decompres-
sion and direct vagal inhibition address this parasympa-
thetic tone. These techniques aim to inhibit
parasympathetic tone, thereby allowing bronchodilation
and decreasing mucus production thereafter. In 2008,
through position changes with a tilt table, Henley
et al
53
demonstrated that parasympathetic responses
overcome sympathetic tone.
Behavioral Mechanism of Treatment
Failure to evaluate and manage existing psychodynamic
issues may exacerbate the symptom complex of
asthma.
65-68
Patients with asthma are at higher risk for
mood disorders and anxiety.
65-68
This risk is even
higher in pediatric and adolescent patients, who may
feel ostracized because of their physical limitations and
frequent absenteeism.
68
Depression and anxiety affect
medication compliance and thus worsen disease. Choi
et al
65
provided evidence of bi-directionality between
the presence or development of asthma in adults and
depression and anxiety. The core osteopathic tenets, of
course, emphasize this equilibrium: “(1) The human
being is a dynamic unit of function, (2) the body pos-
sesses self-regulatory mechanisms that are self-healing
in nature, (3) structure and function are interrelated at
all levels, and (4) rational treatment is based on these
principles.”
69
The ubiquitous Asthma Control Test and
other asthma symptom questionnaires have been sug-
gested to detect emotional issues through lower
scores.
28
A preliminary study by D’Ippolito et al
31
documented significant improvement in depression and
anxiety symptoms among 11 patients with high-
frequency migraine and comorbid mood disorders after
4 OMT sessions (P< .05). Wiegand et al
32
conducted
a randomized, controlled pilot study that indicated statis-
tically significant decrease in self-perceived fatigue
among 1st-year osteopathic medical students receiving
direct OMT. Blumer and Blumer
70
proposed the follow-
ing OMT sequence for anxiety disorder management:
cervical soft tissue/long axis kneeding, cervical high
velocity/low amplitude, sacral decompression, subocci-
pital/occipitoatlantal decompression, doming of the
respiratory diaphragm, and compression of the fourth
ventricle. Relaxation techniques, diaphragmatic breath-
ing, biofeedback, psychological counseling, and patient
and family education may also decrease asthma morbid-
ity from depression and anxiety.
71
Conclusion
Asthma is among the first ailments successfully
managed with OMT in the literature. However, exten-
sive, controlled studies and RCTs applying OMT as an
adjunctive therapy asthma management have not been
pursued. OMT recommendations have been gradually
added to the literature to manage this increasingly
REVIEW
The Journal of the American Osteopathic Association November 2020 |Vol 120 |No. 11 779

prevalent disease, but further larger-scale studies are
warranted to verify their efficacy. The whole-person phil-
osophy, including psychological and behavioral manage-
ment for asthma, is not a novel concept in osteopathic
medicine; the application of these treatment approaches
will continue to yield improvements in asthma
management.
Author Contributions
All authors provided substantial contributions to conceptio n
and design, acquisition of data, or analysis and interpretation of
data; all authors drafted the article or revised it critically for
important intellectual content; all authors gave final
approval of the version of the article to be published; and
all authors agree to be accountable for all aspects of the
work in ensuring that questions related to the accuracy or
integrity of any part of the work are appropriately investigated
and resolved.
References
1. Ti H. Nei Ching Su Wen, The Yellow Emperor’s Classic of Internal
Medicine. Veith I, trans-ed. Baltimore, MD: Williams & Wilkins; 1949.
2. Hippocrates. Corpus Hippocraticum. Potter P. Harvard University
Press; 1938;5(51):285.
3. Ebbell B. The Papyrus Ebers: The Greatest Egyptian Medical
Document. Levin and Munksgaard; 1937.
4. Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular
approaches. Nat Med. 2012;18(5):716-725. doi:10.1038/nm.2678
5. Tabatabaian F. Asthma phenotypes and biomarkers. In Massoud M,
ed. Allergy and Asthma: The Basics to Best Practices. Springer Nature
Switzerland AG; 2019: 275-288.
6. Global Initiative for Asthma (GINA). Global Strategy for Asthma
Management and Prevention, 2019. www.ginasthma.org. Accessed
September 11, 2020.
7. Hanania NA, Wenzel S, Rosen K, et al. Exploring the effects of
omalizumab in allergic asthma: an analysis of biomarkers in the
EXTRA study. Am J Respir Crit Care Med. 2013;187(8):804–811.
doi:10.1164/rccm.201208-1414OC
8. Humbert M, Busse W, Hanania NA, et al. Omalizumab in asthma: an
update on recent developments. J Allergy Clin Immunol Pract. 2014;2
(5):525-536. doi:10.1016/j.jaip.2014.03.010
9. Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe
eosinophilic asthma (DREAM): a multicentre, double-blind,
placebo-controlled trial. Lancet. 2012;380(9842):651-659.
doi:PIIS0140-6736(12)60988-X
10. Haldar P, Brightling CE, Hargadon B, et al. Mepolizumab and
exacerbations of refractory eosinophilic asthma. NEJM. 2009;360
(10):973-984. doi:10.1056/NEJMoa0808991
11. Flood-Page P, Swenson C, Faiferman I, et al. A study to evaluate
safety and efficacy of mepolizumab in patients with moderate
persistent asthma. Am J Respir Crit Care Med. 2007;176
(11):1062-1071. doi:10.1164/rccm.200701-085OC
12. Ortega HG, Liu MC, Pavord ID, et al. Mepolizumab treatment in
patients with severe eosinophilic asthma. N Engl J Med. 2014;371
(13):1198-1207. doi:10.1056/NEJMoa0808991
13. Corren J, Weinstein S, Janka L, Zangrilli J, Garin M. Phase 3 study of
reslizumab in patients with poorly controlled asthma: effects across a
broad range of eosinophil counts. Chest. 2016;150(4):799-810.
doi:10.1016/j.chest.2016.03.018
14. Laviolette M, Gossage DL, Gauvreau G, et al. Effects of benralizumab
on airway eosinophils in asthmatic patients with sputum eosinophilia.
J Allergy Clin Immunol. 2013;132(5):1086-1096. doi:10.1016/j.
jaci.2013.05.020
15. Nowak RM, Parker JM, Silverman RA, et al. A randomized trial of
benralizumab, an antiinterleukin 5 receptor alpha monoclonal antibody,
after acute asthma. Am J Emerg Med. 2015;33(1):14-20. doi:10.1016/j.
ajem.2014.09.036.
16. Wenzel S, Castro M, Corren J, et al. Dupilumab efficacy and safety
in adults with uncontrolled persistent asthma despite use of
medium-to-high-dose inhaled corticosteroids plus a long-acting beta2
agonist: a randomised double-blind placebo-controlled pivotal phase
2b dose-ranging trial. Lancet. 2016; 388(10039):31-44. doi:10.1016/j.
ajem.2014.09.036
17. Castro M, Corren J, Pavord ID, et al. Dupilumab efficacy and safety in
moderate-to-severe uncontrolled asthma. NEJM. 2018;378:2486-2496.
doi:10.1056/NEJMoa1804092
18. Busse WW, Maspero JF, Rabe KF, et al. Liberty asthma QUEST:
phase 3 randomized, double-blind, placebo-controlled, parallel-group
study to evaluate dupilumab efficacy/safety in patients with
uncontrolled, moderate-to-severe asthma. Adv Ther. 2018;35:737.
doi:10.1007/s12325-018-0702-4
19. Rowane WA, Rowane MP. An osteopathic approach to asthma. JAm
Osteopath Assoc. 1999;99(5):259-264. doi:10.7556/
jaoa.1999.99.5.259
20. Jackson KM, Steele KM. Osteopathic treatment of asthma: a literature
review and a call for research. AAOJ. 1999; 9(4):23-27.
21. Moore FE. Discussion of asthma. J Am Osteopath Assoc. 1907;
7:88-89.
22. Oium FN. Cause and cure of asthma. J Am Osteopath Assoc. 1917:
17(3);150-151.
23. Allen TW, D’Alonzo GE. Investigating the role of osteopathic
manipulation in the treatment of asthma. J Am Osteopath Assoc. 1993;
93:654-655,659.
24. Paul FA, Buser BR. Osteopathic manipulative treatment applications
for the emergency department patient. J Am Osteopath Assoc. 1996;
96(7):403-409.
25. Salamon E. Nitric oxide as a possible mechanism for understanding
the therapeutic effects of osteopathic manipulative medicine (review).
Int J Mol Med. 2004;14(3). doi:10.3892/ijmm.14.3.443
26. Posadzki P, Lee MS, Ernst E. Osteopathic manipulative treatment for
pediatric conditions: a systematic review. Pediatrics. 2013;
132:140-152. doi:10.1542/peds.2012-3959
27. Bockenhauer SE, Julliard KN, Lo KS, Huang E, Sheth AM.
Quantifiable effects of osteopathic manipulative techniques on patients
with chronic asthma. J Am Osteopath Assoc. 2002; 371-375.
28. Guiney PA, Chou R, Vianna A, Lovenheim J. Effects of osteopathic
manipulative treatment on pediatric patients with asthma: a
randomized controlled trial. J Am Osteopath Assoc. 2005;105:7-12.
REVIEW
780 The Journal of the American Osteopathic Association November 2020 |Vol 120 |No. 11

29. Lee-Wong M, Karagic M, Gomez S, et al. Adding osteopathic
intervention to albuterol nebulization in ambulatory asthma
exacerbations. Internet J Asthma Allergy Immunol. 2008; 7(2):1-5.
30. Balon J, Crowther ER, Crowther DC, et al. A comparison of active
and simulated chiropractic manipulation as adjunctive treatment for
childhood asthma. NEJM. 1998; 339(15):1013-20. doi:10.1056/
NEJM199810083391501
31. D’Ippolito M, Tramontano M, Buzzi MG. Effects of osteopathic
manipulative therapy on pain and mood disorders in patients with
high-frequency migraine. J Am Osteopath Assoc. 2017;117
(6):365-369. doi:10.7556/jaoa.2017.074
32. Wiegand S, Bianchi W, Quinn TA. Osteopathic manipulative treatment
for self-reported fatigue, stress, and depression in first-year
osteopathic medical students. J Am Osteopath Assoc. 2015;115
(2):84-93. doi:10.7556/jaoa.2015.019
33. Balon JW, Mior SA. Chiropractic care in asthma and allergy. Ann
Allergy Asthma Immunol. 2004; 93(Suppl 1):S55-S60. doi:10.1016/
s1801-1206(10)61487-1
34. Nielsen NH, Bronfort G, Bendix T, et al. Chronic asthma and
chiropractic spinal manipulation: a randomized clinical trial. Clin Exp
Allergy. 1995;25(1):80-88. doi:10.1111/j.1365-2222.1995.tb01006.x.
35. Ernst E. Spinal manipulation for asthma: a systematic review of
randomised clinical trials. Respir Med. 2009;103:1791-1795.
36. Ziment I, Tashkin DP. Alternative medicine for allergy and asthma.
J Allergy Clin Immunol. 2000; 106:603-14. doi:10.1067/
mai.2000.109432
37. Hondras MA, Klaus L, Jones AP. Manual therapy for asthma.
(Protocol). Cochrane Database of Syst Rev. 2005; 2(CD001002).
doi:10.1002/14651858.CD001002
38. Attlee T. Cranio-sacral therapy and the treatment of common childhood
conditions. Health Visitor. 67 7 (1994): 232-234.
39. Still AT. The Philosophy and Mechanical Principles of Osteopathy.
Hudson-Kimberly Pub. Co.; 1902.
40. Still AT. Philosophy of Osteopathy. American Academy of Osteopathy;
1899.
41. Still AT. Asthma. In Osteopathy Research & Practice. The Journal
Printing Co.;1910:94-96.
42. Allen TW, Kelso AF. Osteopathic research and respiratory disease.
J Am Osteopath Assoc. 1980; 79:360.
43. Howell RK, Allen TW, Kappler RE. The influence of osteopathic
manipulative therapy in the management of patients with chronic
obstructive lung disease. J Am Osteopath Assoc. 1975; 74:757-758.
44. Beal M, Morlock J. Somatic dysfunction associated with pulmonary
disease. J Am Osteopath Assoc. 1984;84:179-183.
45. Beal MC. Viscerosomatic reflexes: a review. J Am Osteopath Assoc.
1985; 85:786-799.
46. Wilson PT. The osteopathic treatment of asthma. J Am Osteopath
Assoc. 1946; 45(11):491-492.
47. DiGiovanna EL, Riveria-Martinez S. Pulmonary Applications. In: An
Osteopathic Approach to Diagnosis and Treatment. 3rd ed. Lippincott
Williams & Wilkins; 2005:618-623.
48. Rowane MP, Evans P. Basic Musculoskeletal Manipulation Skills: The
15-Minute Office Encounter (2
nd
edition). American Academy of
Osteopathy; 2019.
49. Morelli-Haskell MA, Sanchez J, Jr. Uncontrolled Asthma. In
Foundations of Osteopathic Medicine.4
th
ed. Lippincott Williams &
Wilkins; 2018:1161-1166.
50. D’Alonzo, GJr., Krachman SL, Foley W, Ettlinger H, Carreiro JE.
Osteopathic Considerations in Pulmonology. In: Foundations of
Osteopathic Medicine. 4th ed. Lippincott Williams & Wilkins; 2018:
1245-1252.
51. Creasy C, Schander A, Orlowski A, Hodge LM. Thoracic and
abdominal lymphatic pump techniques inhibit the growth of S.
pneumoniae bacteria in the lungs of rats. Lymphat Res Biol. 2013;11
(3):183-186. doi:10.1089/lrb.2013.0007
52. Coffman KW. Asthma. J Am Osteopath Assoc. 1902:188-190.
53. Henley CE, Ivins D, Mills M, Wen FK, Benjamin BA. Osteopathic
manipulative treatment and its relationship to autonomic nervous
system activity as demonstrated by heart rate variability: a repeated
measures study. Osteopath Med Prim Care. 2008:2-7. doi:10.1186/
1750-4732-2-7
54. Kuo A, Craig TJ. A retrospective study of risk factors for repeated
admissions for asthma in a rural/suburban university hospital. JAm
Osteopath Assoc. 2001;101(5):S14-7.
55. Downing CH. The Respiratory Tract: Bronchial Asthma. In: Osteopathic
Principles in Disease. American Academy of Osteopathy; 1988:467-70.
56. Nelson KE, Glonek T.Somatic Dysfunction in Osteopathic Family
Medicine (2
nd
Ed). Wolters Kluwer Health. 2015: 92,121.
57. Tazzi P.The behavioral-biopsychosocial model. In: The Five
Osteopathic Models: Rationale, Application, Integration: From an
evidence-based to a person-centered osteopathy. Handspring
Publishing Limited; 2017:370.
58. Carreiro JE. Asthma. In: An Osteopathic Approach To Children (2nd
edition). Churchill Livingstone; 2003:220-221.
59. Chikly B. Contraindications and Precautions for Lymph Drainage
Therapy. In: Silent Waves: Theory and Practice of Lymph Drainage
Therapy: An Osteopathic Lymphatic Technique. International Health &
Healing Inc; 2004:123.
60. Castillo JR, Peters SP, Busse WW. Asthma exacerbations:
pathogenesis, prevention, and treatment. J Allergy Clin Immunol Pract.
2017;5(4):918-927. doi:10.1016/j.jaip.2017.05.001
61. Pepper, AN, Renz H, Casale TB, Garn H. Biologic therapy and novel
molecular targets of severe asthma. J Allergy Clin Immunol Pract.
2017;5(4):909-916. doi:10.1016/j.jaip.2017.04.038
62. Krings JG, McGregor MC, Bacharier LB, Castro M. Biologics for
severe asthma: treatment-specific effects are important in choosing a
specific agent. J Allergy Clin Immunol Pract. 2019;7(5)1379-1392.
doi:10.1016/j.jaip.2019.03.008
63. Moore KL, Dalley AF. Clinically Oriented Anatomy.7
th
ed.
Wolters-Kluwer, Lippincott, Williams & Wilkins:2014.
64. Lewis MJ, Short AL, Lewis KE. Autonomic nervous system control of
the cardiovascular and respiratory systems in asthma. Respir Med.
2006;100(10):1688-1705. doi:10.1016/j.rmed.2006.01.019
65. Choi HG, Kim JH, Park JY, Hwang YI, Jang SH, Jung KS. Association
between asthma and depression: a national cohort study. J Allergy
Clin Immunol Pract. 2019;7:1239-1245. doi:10.1016/j.jaip.2018.10.046
66. Brumpton BM, Leivseth L, Romundstad PR, et al. The joint association
of anxiety, depression, and obesity with incident asthma in adults: The
HUNT Study. Int J Epidemiol. 2013; 42:1455-1463. doi:10.1093/ije/dyt151
REVIEW
The Journal of the American Osteopathic Association November 2020 |Vol 120 |No. 11 781

67. Shankar M, Fagnano M, Blaakman S, Rhee H, Halterman J.
Depressive symptoms among urban adolescents with asthma: a focus
for providers. Acad Pediatr. 2019; 19(6):608-614. doi:10.1016/j.
acap.2018.12.004
68. Katon W, Lozano P, Russo J, Mc Cauley E, Richards on L,
Bush T. The prevalence of DSM- IV anxiety and depressive
disorders in youth wi th asthma compared with con trols.
J Adolesc Health . 2007; 41(5):455-63. doi:10.1016/j.
jadohealth.2 007.05.023
69. Seffinger MA. Philosophy of Osteopathic Medicine. In: Foundations of
Osteopathic Medicine, 4th ed. Wolters Kluwer; 2018:10.
70. Blumer T, Blumer J. Osteopathic approach to anxiety. OFPJ. 2017;
9(4):26-34
71. Toyama M, Hasegawa T, Sakagami T, et al. Depression’sinfluence on
the asthma control test, Japanese version. Allergol Int. 2014; 63
(4):587-594. doi:10.2332/allergolint.14-OA-07080
© 2020 American Osteopathic Association
REVIEW
782 The Journal of the American Osteopathic Association November 2020 |Vol 120 |No. 11