Spine (Phila Pa 1976). 2013 Apr 1;38(7):540-8. doi: 10.1097/BRS.0b013e318275d09c.
Spinal high-velocity low amplitude manipulation in acute nonspecific low back pain: a double-blinded randomized controlled trial in comparison with diclofenac and placebo.von Heymann WJ1, Schloemer P, Timm J, Muehlbauer B.
Author information
AbstractSTUDY DESIGN:A randomized, double-blinded, placebo-controlled, parallel trial with 3 arms.
OBJECTIVE:To investigate in acute nonspecific low back pain (LBP) the effectiveness of spinal high-velocity low-amplitude (HVLA) manipulation compared with the nonsteroidal anti-inflammatory drug diclofenac and with placebo.
SUMMARY OF BACKGROUND DATA:LBP is an important economical factor in all industrialized countries. Few studies have evaluated the effectiveness of spinal manipulation in comparison to nonsteroidal anti-inflammatory drugs or placebo regarding satisfaction and function of the patient, off-work time, and rescue medication.
METHODS:A total of 101 patients with acute LBP (for <48 hr) were recruited from 5 outpatient practices, exclusion criteria were numerous and strict. The subjects were randomized to 3 groups: (1) spinal manipulation and placebo-diclofenac; (2) sham manipulation and diclofenac; (3) sham manipulation and placebo-diclofenac. Outcomes registered by a second and blinded investigator included self-rated physical disability, function (SF-12), off-work time, and rescue medication between baseline and 12 weeks after randomization.
RESULTS:Thirty-seven subjects received spinal manipulation, 38 diclofenac, and 25 no active treatment. The placebo group with a high number of dropouts for unsustainable pain was closed praecox. Comparing the 2 active arms with the placebo group the intervention groups were significantly superior to the control group. Ninety subjects were analyzed in the collective intention to treat. Comparing the 2 intervention groups, the manipulation group was significantly better than the diclofenac group (Mann-Whitney test: P = 0.0134). No adverse effects or harm was registered.
CONCLUSION:In a subgroup of patients with acute nonspecific LBP, spinal manipulation was significantly better than nonsteroidal anti-inflammatory drug diclofenac and clinically superior to placebo.

PMID: 23026869 DOI: 10.1097/BRS.0b013e318275d09c



Spine (Phila Pa 1976). 2011 Aug 15;36(18):1427-37. doi: 10.1097/BRS.0b013e3181f5dfe0.
Does maintained spinal manipulation therapy for chronic nonspecific low back pain result in better long-term outcome?Senna MK1, Machaly SA.
Author information
AbstractSTUDY DESIGN:A prospective single blinded placebo controlled study was conducted.
OBJECTIVE:To assess the effectiveness of spinal manipulation therapy (SMT) for the management of chronic nonspecific low back pain (LBP) and to determine the effectiveness of maintenance SMT in long-term reduction of pain and disability levels associated with chronic low back conditions after an initial phase of treatments.
SUMMARY OF BACKGROUND DATA:SMT is a common treatment option for LBP. Numerous clinical trials have attempted to evaluate its effectiveness for different subgroups of acute and chronic LBP but the efficacy of maintenance SMT in chronic nonspecific LBP has not been studied.
METHODS:Sixty patients, with chronic, nonspecific LBP lasting at least 6 months, were randomized to receive either (1) 12 treatments of sham SMT over a 1-month period, (2) 12 treatments, consisting of SMT over a 1-month period, but no treatments for the subsequent 9 months, or (3) 12 treatments over a 1-month period, along with "maintenance spinal manipulation" every 2 weeks for the following 9 months. To determine any difference among therapies, we measured pain and disability scores, generic health status, and back-specific patient satisfaction at baseline and at 1-, 4-, 7-, and 10-month intervals.
RESULTS:Patients in second and third groups experienced significantly lower pain and disability scores than first group at the end of 1-month period (P = 0.0027 and 0.0029, respectively). However, only the third group that was given spinal manipulations (SM) during the follow-up period showed more improvement in pain and disability scores at the 10-month evaluation. In the nonmaintained SMT group, however, the mean pain and disability scores returned back near to their pretreatment level.
CONCLUSION:SMT is effective for the treatment of chronic nonspecific LBP. To obtain long-term benefit, this study suggests maintenance SM after the initial intensive manipulative therapy.

PMID: 21245790 DOI: 10.1097/BRS.0b013e3181f5dfe0



https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5106443/

J Chiropr Med. 2016 Dec;15(4):259-271. Epub 2016 Oct 18.
A Narrative Review of Lumbar Fusion Surgery With Relevance to Chiropractic Practice.Daniels CJ1, Wakefield PJ1, Bub GA1, Toombs JD1.
Author information
AbstractOBJECTIVE:The purpose of this narrative review was to describe the most common spinal fusion surgical procedures, address the clinical indications for lumbar fusion in degeneration cases, identify potential complications, and discuss their relevance to chiropractic management of patients after surgical fusion.
METHODS:The PubMed database was searched from the beginning of the record through March 31, 2015, for English language articles related to lumbar fusion or arthrodesis or both and their incidence, procedures, complications, and postoperative chiropractic cases. Articles were retrieved and evaluated for relevance. The bibliographies of selected articles were also reviewed.
RESULTS:The most typical lumbar fusion procedures are posterior lumbar interbody fusion, anterior lumbar interbody fusion, transforaminal interbody fusion, and lateral lumbar interbody fusion. Fair level evidence supports lumbar fusion procedures for degenerative spondylolisthesis with instability and for intractable low back pain that has failed conservative care. Complications and development of chronic pain after surgery is common, and these patients frequently present to chiropractic physicians. Several reports describe the potential benefit of chiropractic management with spinal manipulation, flexion-distraction manipulation, and manipulation under anesthesia for postfusion low back pain. There are no published experimental studies related specifically to chiropractic care of postfusion low back pain.
CONCLUSIONS:This article describes the indications for fusion, common surgical practice, potential complications, and relevant published chiropractic literature. This review includes 10 cases that showed positive benefits from chiropractic manipulation, flexion-distraction, and/or manipulation under anesthesia for postfusion lumbar pain. Chiropractic care may have a role in helping patients in pain who have undergone lumbar fusion surgery.



Drug Alcohol Depend. 2017 Apr 1;173 Suppl 1:S11-S21. doi: 10.1016/j.drugalcdep.2016.12.002.
Providing chronic pain management in the "Fifth Vital Sign" Era: Historical and treatment perspectives on a modern-day medical dilemma.Tompkins DA1, Hobelmann JG2, Compton P3.
Author information
AbstractBACKGROUND:Over 100 million Americans are living with chronic pain, and pain is the most common reason that patients seek medical attention. Despite the prevalence of pain, the practice of pain management and the scientific discipline of pain research are relatively new fields compared to the rest of medicine - contributing to a twenty-first century dilemma for health care providers asked to relieve suffering in the "Fifth Vital Sign" era.
METHODS:This manuscript provides a narrative review of the basic mechanisms of chronic pain and history of chronic pain management in the United States - including the various regulatory, health system and provider factors that contributed to the decline of multidisciplinary pain treatment in favor of the predominant opioid treatment strategy seen today. Multiple non-opioid pain treatment strategies are then outlined. The manuscript concludes with three key questions to help guide future research at the intersection of pain and addiction.
CONCLUSIONS:The assessment and treatment of chronic pain will continue to be one of the most common functions of a health care provider. To move beyond an over reliance on opioid medications, the addiction and pain research communities must unite with chronic pain patients to increase the evidence base supporting non-opioid analgesic strategies.
Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Spine (Phila Pa 1976). 2013 Apr 1;38(7):540-8. doi: 10.1097/BRS.0b013e318275d09c.
Spinal high-velocity low amplitude manipulation in acute nonspecific low back pain: a double-blinded randomized controlled trial in comparison with diclofenac and placebo.von Heymann WJ1, Schloemer P, Timm J, Muehlbauer B.
Author information
AbstractSTUDY DESIGN:A randomized, double-blinded, placebo-controlled, parallel trial with 3 arms.
OBJECTIVE:To investigate in acute nonspecific low back pain (LBP) the effectiveness of spinal high-velocity low-amplitude (HVLA) manipulation compared with the nonsteroidal anti-inflammatory drug diclofenac and with placebo.
SUMMARY OF BACKGROUND DATA:LBP is an important economical factor in all industrialized countries. Few studies have evaluated the effectiveness of spinal manipulation in comparison to nonsteroidal anti-inflammatory drugs or placebo regarding satisfaction and function of the patient, off-work time, and rescue medication.
METHODS:A total of 101 patients with acute LBP (for <48 hr) were recruited from 5 outpatient practices, exclusion criteria were numerous and strict. The subjects were randomized to 3 groups: (1) spinal manipulation and placebo-diclofenac; (2) sham manipulation and diclofenac; (3) sham manipulation and placebo-diclofenac. Outcomes registered by a second and blinded investigator included self-rated physical disability, function (SF-12), off-work time, and rescue medication between baseline and 12 weeks after randomization.
RESULTS:Thirty-seven subjects received spinal manipulation, 38 diclofenac, and 25 no active treatment. The placebo group with a high number of dropouts for unsustainable pain was closed praecox. Comparing the 2 active arms with the placebo group the intervention groups were significantly superior to the control group. Ninety subjects were analyzed in the collective intention to treat. Comparing the 2 intervention groups, the manipulation group was significantly better than the diclofenac group (Mann-Whitney test: P = 0.0134). No adverse effects or harm was registered.
CONCLUSION:In a subgroup of patients with acute nonspecific LBP, spinal manipulation was significantly better than nonsteroidal anti-inflammatory drug diclofenac and clinically superior to placebo.

PMID: 23026869 DOI: 10.1097/BRS.0b013e318275d09c



Spine (Phila Pa 1976). 2011 Aug 15;36(18):1427-37. doi: 10.1097/BRS.0b013e3181f5dfe0.
Does maintained spinal manipulation therapy for chronic nonspecific low back pain result in better long-term outcome?Senna MK1, Machaly SA.
Author information
AbstractSTUDY DESIGN:A prospective single blinded placebo controlled study was conducted.
OBJECTIVE:To assess the effectiveness of spinal manipulation therapy (SMT) for the management of chronic nonspecific low back pain (LBP) and to determine the effectiveness of maintenance SMT in long-term reduction of pain and disability levels associated with chronic low back conditions after an initial phase of treatments.
SUMMARY OF BACKGROUND DATA:SMT is a common treatment option for LBP. Numerous clinical trials have attempted to evaluate its effectiveness for different subgroups of acute and chronic LBP but the efficacy of maintenance SMT in chronic nonspecific LBP has not been studied.
METHODS:Sixty patients, with chronic, nonspecific LBP lasting at least 6 months, were randomized to receive either (1) 12 treatments of sham SMT over a 1-month period, (2) 12 treatments, consisting of SMT over a 1-month period, but no treatments for the subsequent 9 months, or (3) 12 treatments over a 1-month period, along with "maintenance spinal manipulation" every 2 weeks for the following 9 months. To determine any difference among therapies, we measured pain and disability scores, generic health status, and back-specific patient satisfaction at baseline and at 1-, 4-, 7-, and 10-month intervals.
RESULTS:Patients in second and third groups experienced significantly lower pain and disability scores than first group at the end of 1-month period (P = 0.0027 and 0.0029, respectively). However, only the third group that was given spinal manipulations (SM) during the follow-up period showed more improvement in pain and disability scores at the 10-month evaluation. In the nonmaintained SMT group, however, the mean pain and disability scores returned back near to their pretreatment level.
CONCLUSION:SMT is effective for the treatment of chronic nonspecific LBP. To obtain long-term benefit, this study suggests maintenance SM after the initial intensive manipulative therapy.

PMID: 21245790 DOI: 10.1097/BRS.0b013e3181f5dfe0



https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5106443/

J Chiropr Med. 2016 Dec;15(4):259-271. Epub 2016 Oct 18.
A Narrative Review of Lumbar Fusion Surgery With Relevance to Chiropractic Practice.Daniels CJ1, Wakefield PJ1, Bub GA1, Toombs JD1.
Author information
AbstractOBJECTIVE:The purpose of this narrative review was to describe the most common spinal fusion surgical procedures, address the clinical indications for lumbar fusion in degeneration cases, identify potential complications, and discuss their relevance to chiropractic management of patients after surgical fusion.
METHODS:The PubMed database was searched from the beginning of the record through March 31, 2015, for English language articles related to lumbar fusion or arthrodesis or both and their incidence, procedures, complications, and postoperative chiropractic cases. Articles were retrieved and evaluated for relevance. The bibliographies of selected articles were also reviewed.
RESULTS:The most typical lumbar fusion procedures are posterior lumbar interbody fusion, anterior lumbar interbody fusion, transforaminal interbody fusion, and lateral lumbar interbody fusion. Fair level evidence supports lumbar fusion procedures for degenerative spondylolisthesis with instability and for intractable low back pain that has failed conservative care. Complications and development of chronic pain after surgery is common, and these patients frequently present to chiropractic physicians. Several reports describe the potential benefit of chiropractic management with spinal manipulation, flexion-distraction manipulation, and manipulation under anesthesia for postfusion low back pain. There are no published experimental studies related specifically to chiropractic care of postfusion low back pain.
CONCLUSIONS:This article describes the indications for fusion, common surgical practice, potential complications, and relevant published chiropractic literature. This review includes 10 cases that showed positive benefits from chiropractic manipulation, flexion-distraction, and/or manipulation under anesthesia for postfusion lumbar pain. Chiropractic care may have a role in helping patients in pain who have undergone lumbar fusion surgery.



Drug Alcohol Depend. 2017 Apr 1;173 Suppl 1:S11-S21. doi: 10.1016/j.drugalcdep.2016.12.002.
Providing chronic pain management in the "Fifth Vital Sign" Era: Historical and treatment perspectives on a modern-day medical dilemma.Tompkins DA1, Hobelmann JG2, Compton P3.
Author information
AbstractBACKGROUND:Over 100 million Americans are living with chronic pain, and pain is the most common reason that patients seek medical attention. Despite the prevalence of pain, the practice of pain management and the scientific discipline of pain research are relatively new fields compared to the rest of medicine - contributing to a twenty-first century dilemma for health care providers asked to relieve suffering in the "Fifth Vital Sign" era.
METHODS:This manuscript provides a narrative review of the basic mechanisms of chronic pain and history of chronic pain management in the United States - including the various regulatory, health system and provider factors that contributed to the decline of multidisciplinary pain treatment in favor of the predominant opioid treatment strategy seen today. Multiple non-opioid pain treatment strategies are then outlined. The manuscript concludes with three key questions to help guide future research at the intersection of pain and addiction.
CONCLUSIONS:The assessment and treatment of chronic pain will continue to be one of the most common functions of a health care provider. To move beyond an over reliance on opioid medications, the addiction and pain research communities must unite with chronic pain patients to increase the evidence base supporting non-opioid analgesic strategies.
Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Control and Prevention (CDC), in 2014, almost 2 million Americans abused or were dependent on prescription opioids. However, there is not a blanket solution to this epidemic because the factors that surround the prescription Opioid overuse and abuse are often complicated and complex in nature.
 
Many of these factors reach far beyond a mechanical, physical pain. However, for acute, subacute musculoskeletal and chronic non-cancer pain (CNCP) syndromes, the UVCA supports a non-pharmacological or conservative approach as a first-line therapy towards resolution for the patient. In March 2016, The CDC's Guideline for Prescribing Opioids for Chronic Pain was released.  In the document, a recommendation for first-line non-pharmacological treatment was made. The CDC's recommendation is that "multimodal and multidisciplinary therapies (e.g., therapies that combine exercise and related therapies with psychologically based approaches) can help reduce pain and improve function more effectively than single modalities." The CDC is urging health care providers to reduce the use of opioids in favor of safe alternatives.
 
It is the opinion of the UVCA that Chiropractors are an effective deliverer of this type of "multimodal and multidisciplinary” care. It is also the opinion of the UVCA that Chiropractors can effectively and efficiently manage a great percentage of these cases to reasonable resolution for the patient. With low-risk outcomes and an opportunity for the patient to live with less pain, the UVCA urges the public to strongly consider utilization of Chiropractic as a viable option for acute, subacute musculoskeletal, and chronic non-cancer pain (CNCP) syndromes.
 
Resources 

• Virginia Board of Medicine Creates New Opioid Prescription Guidelines: http://www.richmond.com/life/health/va-board-creates-new-opioid-prescription-guidelines/article_34ceace4-24f7-5125-9445-680f6f7bede4.html
• “The Cost of Prescription Painkillers” Video from The Chiropractic Society of Wisconsin: https://vimeo.com/187921433
• “Chiropractic: A Safer Solution to the Opioid Epidemic” Video from the Tennessee Chiropractic Association:  http://www.tnchiro.com/videos/tennessee-chiropractic-association-chiropractic-a-safer-solution-to-the-opioid-epidemic/
• “Medical Journal Recommends Spinal Manipulation as a Primary Treatment for Low Back Pain” [Click Here]
• Clinical Compass (CCGPP):
  o   “Integration of Evidence Based Alternatives to Address the Opioid Crisis” - An editable PowerPoint Presentation for use by DCs to educate their patients.  [Part I] [Part II]
  o   Variety of related papers:  http://clinicalcompass.org/ccgpp/opioid-resources
• The Ohio Governor’s Task Force: Acute Pain Infographic from Ohio State Chiropractic Association [Click Here]
• American Chiropractic Association:  “Chiropractic and the Opioid Epidemic: Rethinking Our Approach to Pain” at http://www.acatoday.org/Patients-Why-Choose-Chiropractic-Chiropractic-and-the-Opioid-Epidemic
• Foundation for Chiropractic Progress:  “F4CP Opioids Toolkit 1.0”
  o   Complete toolkit at http://www.f4cp.com/resources/tool-kit/F4CP_Opioids_1.0_Toolkit.pdf
  o   White paper “Chiropractic: A Safer Strategy than Opioids” at http://www.f4cp.com/f4cp_opioid_white_paper.pdf
• CDC Releases Guideline for Prescribing Opioids for Chronic Pain:  https://www.cdc.gov/media/releases/2016/p0315-prescribing-opioids-guidelines.html
• From Unified VCA Supporting Supplier Member Kaizenovation Advisors, Created for The Chiropractic Summit:http://www.kaizenovationadvisers.com/blog/opioid-crisis-toolkit

News Release

• UVCA News Release RE Opioid Crisis 3-30-17
• Seniors’ Use of Opioids Underscores Need for Drug-Free Chiropractic Care, Advises Unified Virginia Chiropractic Association
• Association Between Utilization of Chiropractic Services for Treatment of Low-Back Pain and Use of Prescription Opioids

​https://vachiro.site-ym.com/?page=TheOpioidsCrisis

Epidemiology and misdiagnosis EIB is commonly diagnosed in active individuals who report symptoms of dyspnoea, fatigue or inferior performance during exercise. EIB occurs across ages and fitness levels. The prevalence is reported prevalence ranges from ∼10 to >50% or greater in competitive athletes. Guidelines for diagnosis and management of asthma and EIB are well established. However, asthma and EIB are frequently misdiagnosed in clinical practice, in part because diagnosis is typically made based on symptoms alone
(as in the previous examples), rather than strictly adhering to proper diagnostic algorithms. The signs and symptoms of EIB are very nonspecific and therefore have poor clinical diagnostic value. Inappropriate diagnosis and management of EIB can lead to continuation or progression of symptoms, which may lead to impaired performance, discontinuation of sport or in extreme cases, sudden death. Case reports abound in which a serious condition was initially missed due to a misdiagnosis of EIB. A recent multicenter study found that adherence to asthma guidelines was quite poor for children and adults in primary care centers throughout the USA
 
A couple examples of history questions and their purpose are:
Do you ever feel lightheaded or dizzy while experiencing these symptoms?
These symptoms suggests the individual may be developing hypoxaemia (e.g. inadequate alveolar gas exchange) or inadequate blood flow to the brain during exercise (e.g. inadequate blood pressure or vertebrobasilar artery insufficiency)
Aside from your respiratory symptoms, have you been feeling unusually tired or exhausted when you are not exercising?
Overtraining syndrome and infectious disease (e.g. Lyme disease, mononucleosis or influenza) are common and may contribute to general fatigue, malaise and unusual soreness Emotional illness (e.g. clinical depression) may also be considered Less common conditions that influence metabolic dysfunction (e.g. mitochondrial myopathy) may also be considered
Do you have unusual muscle or joint pain, beyond what you would normally expect from exercise? Exercise-specific symptoms How long have you been doing the type of exercise in which you experience these symptoms?
It is important to understand the individual’s reference point for the dyspnoeic symptoms reported; for instance, an individual with a long history of recreational running is likely to be familiar with their ventilatory response during running, whereas they may feel unusually out of breath in unaccustomed forms exercise with different neuromuscular demands (e.g. swimming) or intensity (e.g. sprint-interval sports like soccer


EUROPEAN CLINICAL RESPIRATORY JOURNAL
REVIEW ARTICLE Exercise and asthma: an overview
Stefano R. Del Giacco, Davide Firinu, Leif Bjerme, Kai-Ha ˚kon, M. Aresu


The terms ‘exercise-induced asthma’ (EIA) and ‘exercise-induced bronchoconstriction’ (EIB) are often used interchangeably to describe symptoms of asthma such as cough, wheeze, or dyspnoea provoked by vigorous physical activity. In this review, we refer to EIB as the broncho constrictive response and to EIA when bronchoconstriction is associated with asthma symptoms. EIB is a common occurrence for most of the asthmatic patients, but it also affects more than 10% of otherwise healthy individuals as shown by epidemiological studies. EIA and EIB have a high prevalence also in elite athletes, especially within endurance type of sports, and an athlete’s asthma phenotype has been described. However, the occurrence in elite athletes shows that EIA/EIB, if correctly managed, may not impair physical activity and tops ports performance. The pathogenic mechanisms of EIA/EIB classically involve both osmolar and vascular changes in the airways in addition to cooling of the airways with parasympathetic stimulation. Airways inflammation plays a fundamental role in EIA/EIB. Diagnosis and pharmacological management must be carefully performed, with particular consideration of current anti-doping regulations, when caring for athletes. Based on the demonstration that the inhaled asthma drugs do not improve performance in healthy athletes, the doping regulations are presently much less strictthanpreviously. Somesportsareatahigherasthmari skthanothers, probablyduetoahighenvironmenta l exposure while performing the sport, with swimming and chlorine exposure during swimming as one example. It is considered very important for the asthmatic child and adolescent to master EIA/EIB to be able to participate in physical activity on an equal level with their peers, and a precise early diagnosis with optimal treatment follow-up is vital in this aspect. In addition, surprising recent preliminary evidences offer new perspectives for moderate exercise as a potential therapeutic tool for asthmatics.


In addition, a recent report raised attention on a potential loss of bronchoprotection for athletes using LABAs, independent from the Arg16Gly polymorphisms that may affect the efficacy of these medications.
Non-pharmacological measures are also of importance: nasal breathing and pre-exercise warm-ups (15-30 sec exertions alternate with 60-90 sec rest) followed by a warm-down segment are suggested, together with anti-cold masks for cold environments.






Perception of Exercise-Induced Bronchoconstriction in College Athletes
David M Burnett PhD RRT AE-C, John P Vardiman PhD ATC, Jake A Deckert MSc, Jaimie L Ward and Matthew R Sharpe MD


BACKGROUND: Exercise-induced bronchoconstriction (EIB) can lead to long-term respiratory illness and even death. EIB prevalence rates are both high and variable in college athletes. Also, prevalence rates may be underestimated due to ineffective screening.






CONFERENCE PROCEEDINGS Section 2.
Exercise-Induced Bronchospasm: Albuterol versus Montelukast Highlights of the Asthma Summit 2009: Beyond the Guidelines
Gene Colice, MD, FCCP, and William J. Calhoun, MD, FACP, FCCP, FAAAAI, FACAAI2


A peculiar feature of EIB is the so-called refractory period. If exercise is repeated within 1 to 3 hours, there will be less of an EIB response. This has led some to advocate a warm-up for asthma patients before full intensity exercise. Whether late bronchoconstriction, defined as that occurring 4 to 6 hours after exercise, is a part of EIB remains in debate. Although there are numerous theories about why EIB occurs, the underlying mechanisms of EIB are not clear. Several drugs and some nonpharmacological approaches seem to be effective in protecting against, or relieving symptoms of, EIB. The National Asthma Education and Prevention Program Third Expert Panel Report (EPR-3) recommends use of either short-acting or long acting inhaled  2-agonists as the preferred preventive treatment for EIB.4 Using these agents before exercise will effectively prevent EIB in more than 80% of patients. The EPR-3 guidelines do note that leukotriene receptor antagonists (LTRA) can attenuate EIB in up to 50% of patients, but the onset of the protective effect of LTRAs occurs only hours after administration of these agents.4 There are clear advantages of albuterol, or other short acting inhaled  2-agonists, over montelukast in managing EIB. The protective effect of albuterol against EIB is apparent quickly, unlike LTRAs that must be given hours before exercise to prevent EIB. Albuterol can be administered 15 to 30 minutes before exercise in both children and adults to prevent exercise-related symptoms.5–9 In addition, albuterol seems to more effectively prevent EIB than montelukast. In a
direct comparative study patients with proven EIB were treated with either montelukast for 3–7 days or albuterol 15 minutes preexercise. Albuterol virtually eliminated the postexercise fall in FEV1 in these patients, whereas montelukast provided only a mild attenuating effect8 (Fig. 2). A preexercise warm up has also been shown to not be as effective as albuterol pretreatment for preventing EIB.5 Albuterol can also be used as a rescue medication if symptoms of EIB occur despite use of preventive measures.9 This is another differentiating factor between albuterol and LTRAs. Of 3 studies that evaluated the effect of single-dose montelukast in preventing EIB, 2 specified that albuterol was to be used for rescue therapy if patients became symptomatic during exercise,10,11 and one included use of short-acting  -agonists as rescue therapy as a prespecified secondary end point.12 A total of 31% of the patients in one study who used montelukast as prophylaxis experienced postexercise falls in FEV1 exceeding 15%.10 This degree of bronchospasm would usually be treated with a rescue medication, specifically albuterol. Similarly, in the other study 17% of patients experienced declines of more than 20%.11 In the third study, 6% of patients were given albuterol for rescue despite being pretreated with montelukast to prevent EIB.12 From the practical, patient care perspective, asthma patients using montelukast to prevent EIB should still have albuterol on hand to treat unanticipated episodes of EIB that might still occur. There are concerns about the use of albuterol in EIB. Tachyphylaxis is a concern with the regular use of albuterol, and the question remains whether using albuterol pretreatment for exercise daily results in tachyphylaxis that might make therapy less effective. In one study in which patients took albuterol or placebo for 6 to 10 days and exercised without pretreatment, the exercise-induced fall in FEV1 was greater among the group using albuterol than it was among the placebo group.13 In this study, though, treatment with albuterol after EIB developed effectively improved lung function. Similar results were seen in another study where patients took albuterol 4 times a day for 7 days.9 However, in this study albuterol administered immediately before exercise was still effective in preventing EIB.9 It should be emphasized, though, the guidelines on the management of asthma make it clear that regular use of albuterol is not recommended.4 Tachyphylaxis to the effects of albuterol might also occur if patients were regularly using an inhaled long acting  2-agonist. Regular use of salmeterol has been reported to reduce the effect of albuterol treatment to protect against methacholine-induced bronchoconstriction. Nelson et al, though, showed that the acute bronchodilator response to albuterol was maintained in asthma patients who were either inhaled corticosteroid (ICS)naive or receiving ICS, regardless of regular salmeterol use. However, another study found that the effect of albuterol against EIB was reduced in asthmatic patients who regularly used a combination of ICS and long-acting  -agonists.16 Overall, it is unclear whether the regular use of an inhaled long-acting  2-agonist will reduce either the protective or treatment effect of albuterol in EIB. Any possible decreased protection by albuterol for EIB should be carefully weighed against the overall clinical benefits achieved from using combination therapy with an ICS and an inhaled long-acting
2-agonist.


MONTELUKAST AND EXERCISE-INDUCED ASTHMA: COMMENTARY BY WILLIAM J. CALHOUN, MD, FACP, FCCP, FAAAAI, FACAAI


Taken on a regular once-daily basis, the LTRA montelukast has been shown to improve the exercise-induced deficit in lung function: blunting the early fall in FEV1, reducing the area under the curve (AUC), and decreasing the time to recovery of normal lung function. Similarly, montelukast has been demonstrated to reduce the fall in FEV1 after eucapnic voluntary hyperventilation, an experimental model of EIB that focuses on the cooling and drying of the airway. The benefit of montelukast against exercise challenge can be seen as early as 3 days on regular treatment. Specific challenge studies have reported improvements in lung function as soon as 2 hours after a single dose. The positive effects of montelukast therapy can persist for up to 8 weeks after discontinuation, suggesting that treatment induces physiological changes in the airway. No tachyphylaxis or loss of protection have been observed. For the most part, montelukast provides comparable (and sometimes even superior) protection to other approaches used to address EIB. For example, in children with mild asthma both montelukast and fitness training reduced BHR and also decreased the incidence of EIB by 50%. Another randomized study in atopic children reported a 54% reduction in the maximum postexercise fall in FEV1 with montelukast (5 or 10 mg once daily) compared with reductions of 52, 32, and 24% for montelukast  budesonide (100

 g bid), budesonide alone, and budesonide  formoterol (100
 g/4.5
 g bid), respectively; patients treated with placebo showed an increase of 9%. In a study in adults with EIA single doses of montelukast (10 mg) and salmeterol (42
 g) provided comparable prophylaxis against EIB more than 12 hours, reducing the fall in FEV1 by [1]70% (P
 0.001 for salmeterol, and P
 0.001 for montelukast).28 The difference between the 2 agents was an onset of action within 10 minutes after challenge for salmeterol compared with an onset within 1 hour for montelukast. A comparison of the effects of regular use of salmeterol (50
 g bid) and montelukast (10 mg qd) on EIB more than 8 weeks in 197 patients with mild asthma reported few differences between the 2 treatments, but overall, montelukast provided slightly better control with no tolerance evident and fewer adverse events.29 The benefit of montelukast compared with albuterol, however, is not as clear cut. In a crossover study of 11 children (7–17 years), EIB was better controlled by pretreatment with 2 puffs of albuterol than with 3–7 days of daily treatment with montelukast (5 or 10 mg).  Albuterol significantly reduced EIB in 100% of the patients, compared with 55% for montelukast. Thus, a dose of albuterol given immediately before exercise might be superior to daily dosing with montelukast. However, other data suggest that montelukast preserves the bronchodilator responsiveness to albuterol. Some patients may benefit from using both, and additional study is warranted to address this.



DISCUSSION Dr. Calhoun: Obviously, it is scientifically untenable for either of us to take a position that the only appropriate treatment for EIB is either montelukast or albuterol. However, I would like to emphasize three things. First, I think the question of tachyphylaxis is important. Dr. Colice presented data showing that people who had regular albuterol for a week had a larger decrement in FEV1 postexercise than those who were on placebo. Four times a day albuterol is not a lot, it does not saturate the beta receptors continuously; so, to the extent that patients needed more and more and more albuterol, the issue of tachyphylaxis is significant. Second, there are things that are unmeasured. For example, activation of the counter-regulatory phospholipase C pathway with chronic stimulation of the beta receptors is probably not good.
Dr. Colice: Yes, the data show that if a patient uses albuterol regularly, the fall in FEV1 with EIB might actually be enhanced. However, when these patients then took a dose of albuterol preexercise, it still completely eliminated the fall in FEV1 during exercise.

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infections, and adverse pregnancy outcomes in addition to the classical bone disorders of rickets and osteomalacia. Furthermore, investigators have found adequate repletion and increased intakes of vitamin D to be associated with reduced all-cause mortality rates. These findings have been supported by the limited number of properly conducted randomized controlled trials (RCTs) that used more than 400 IU/day of vitamin D. This review presents an overview of the role of vitamin D for the promotion of health for the more important vitamin D-related diseases and conditions. Serum 25-hydroxyvitamin D concentrations of 30-60 ng/ml, corresponding to oral intake or skin production of 1,000-4,000 IU/day of vitamin D, appear necessary in adults for avoidance of hypovitaminosis D-related ill health. People of all ages are encouraged to obtain more vitamin D from judicious exposure to sunshine (for ultraviolet B [UVB] irradiation) or from regular vitamin D supplements because dietary sources do not provide sufficient vitamin D to prevent any health risks other than those of rickets and osteomalacia.



Ann N Y Acad Sci. 2016 Mar;1367(1):57-63. doi: 10.1111/nyas.13058.Vitamin D in dementia prevention.Annweiler C1,2,3.Author informationAbstractBeyond effects on bone health, vitamin D exerts effects on a variety of target organs, including the brain. The discussion herein presents the state of the art in research on the neurological role of vitamin D and clinical implications among older adults, including implications for dementia onset and progression. Some of the neurosteroid actions of vitamin D include regulation of calcium homeostasis, clearance of amyloid-β peptide, antioxidant and anti-inflammatory effects, and possible protection against the neurodegenerative mechanisms associated with Alzheimer's disease (AD). The correction of age-related hypovitaminosis D and cognitive decline has been reported by various cross-sectional and longitudinal studies reporting associations of lower vitamin D concentrations with brain changes and poorer cognition, specifically with respect to executive dysfunction. Epidemiological studies have consistently shown an association between inadequate dietary intake of vitamin D and cognitive disorders, including greater AD risk. Although there have not been any randomized placebo-controlled trials conducted to examine the effectiveness of vitamin D supplementation to prevent AD, several nonrandomized controlled studies have found that older adults experienced cognitive improvements after 1-15 months of vitamin D supplementation. Therefore, it appears crucial to maintain vitamin D concentrations at sufficiently high levels in order to slow, prevent, or improve neurocognitive decline.
© 2016 New York Academy of Sciences.


J Alzheimers Dis. 2016 May 11;53(2):419-44. doi: 10.3233/JAD-150943.Vitamin D, Cognition and Alzheimer's Disease: The Therapeutic Benefit is in the D-Tails.Landel V1, Annweiler C2,3, Millet P1,4, Morello M1,5,6, Féron F1.Author informationAbstractSince its discovery during the epidemic of rickets in the early 1920s, the physiological effects of vitamin D on calcium/phosphorus homeostasis have been thoroughly studied. Along with the understanding of its actions on skeletal diseases and advances in cellular and molecular biology, this misnamed vitamin has gained attention as a potential player in a growing number of physiological processes and a variety of diseases. During the last 25 years, vitamin D has emerged as a serious candidate in nervous system development and function and a therapeutic tool in a number of neurological pathologies. More recently, experimental and pre-clinical data suggest a link between vitamin D status and cognitive function. Human studies strongly support a correlation between low levels of circulating 25-hydroxyvitamin D (25(OH)D) and cognitive impairment or dementia in aging populations. In parallel, animal studies show that supplementation with vitamin D is protective against biological processes associated with Alzheimer's disease (AD) and enhances learning and memory performance in various animal models of aging and AD. These experimental observations support multiple mechanisms by which vitamin D can act against neurodegenerative processes. However, clinical interventional studies are disappointing and fail to associate increased 25(OH)D levels with improved cognitive outcomes. This review collects the current available data from both animal and human studies and discusses the considerations that future studies examining the effects of vitamin D status on neurocognitive function might consider.
Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4969697/ 




Aging Dis. 2012 Aug;3(4):313-29. Epub 2012 Jun 6.
The problems of vitamin d insufficiency in older people.

Boucher BJ1.Author informationAbstractThis report reviews evidence on disorders related to inadequate vitamin D repletion in older people. Vitamin D is as essential for bone health in adults as in children, preventing osteomalacia and muscle weakness and protecting against falls and low-impact fractures. Vitamin D is provided by skin synthesis by UVB-irradiation from summer sunshine and to a small extent by absorption from food. However, these processes become less efficient with age. Loss of mobility or residential care restricts solar exposure. Reduced appetite and financial problems often add to these problems. Thus, hypovitaminosis D is common world-wide, but is more common and more severe in older people. Non-classical effects of vitamin D, depending on serum circulating 25-hydroxyvitamin D concentrations, are present in most non-bony tissues; disorders associated with hypovitaminosis D include increased risks of sepsis [bacterial, mycobacterial and viral], cardiovascular and metabolic disorders [e.g. hyperlipidemia, type 2 diabetes mellitus, acute vascular events, dementia, stroke and heart failure]. Many cancer risks are associated with vitamin D inadequacy, though causality is accepted only for colo-rectal cancer. Maintenance of repletion in healthy older people requires intakes of ≥800IU/day [20μg], as advised by the Institute of Medicine [IOM], but achieving such intakes usually requires supplementation. Excessive intakes are dangerous, especially in undiagnosed primary hyperparathyroidism or sarcoidosis, but the IOM finds doses <4000 IU/day are safe. Many experts suggest that ≥1000-2000 IU [25-50μg] of vitamin D daily is necessary for older people, especially when independence is lost, or hypovitaminosis D could add to the clinical problem[s]. Much higher doses than these are needed for treatment of established deficiency or insufficiency.


Increased telomerase activity and vitamin D supplementation in overweight African Americans H Zhu1 , D Guo1 , K Li2 , J Pedersen-White3 , IS Stallmann-Jorgensen1 , Y Huang1 , S Parikh1 , K Liu4 and Y Dong1 International Journal of Obesity (2011), 1 -- 5 & 2011 Macmillan Publishers Limited All rights reserved 0307-0565/11 www.nature.com/ijo ​