Thalasemia

Thalasemia

The major hemoglobin in adults is hemoglobin A, which is a tetramer consisting of two pairs of globin polypeptide chains: one pair of alpha chains; and one pair of beta chains. In normal subjects, globin chain synthesis is very tightly controlled so that the ratio of production of alpha to non-alpha chains is 1.00 ± 0.05. There are two copies of the alpha globin gene on chromosome 16. A single beta globin gene resides on chromosome 11 adjacent to genes encoding the beta-like globin chains, delta and gamma.

Thalassemia refers to a spectrum of diseases characterized by reduced or absent production of one or more globin chains. Beta thalassemia is due to impaired production of beta globin chains, which leads to a relative excess of alpha globin chains. These excess alpha globin chains are unstable, incapable of forming soluble tetramers on their own, and precipitate within the cell, leading to a variety of clinical manifestations. The degree of alpha globin chain excess determines the severity of subsequent clinical manifestations, which are profound in patients homozygous for impaired beta globin synthesis and much less pronounced in heterozygotes who generally have minimal or mild anemia and no symptoms. 

Alpha thalassemia, in comparison, is due to impaired production of alpha globin chains, which leads to a relative excess of beta globin chains. The toxicity of the excess beta globin chains in alpha thalassemia on the red cell membrane skeleton appears to be less than that of the excess partially oxidized alpha globin chains in beta thalassemia. This probably explains why the clinical manifestations are generally less severe in alpha compared with beta thalassemia of comparable genetic severity (except for homozygous alpha (0) thalassemia, which is incompatible with extrauterine life, leading to hydrops fetalis and/or death shortly after delivery).

Certain clinical terms are used to describe the phenotypic expression of beta thalassemia:

Beta (0) thalassemia — Beta (0) thalassemia refers to mutations of the beta globin locus that result in the absence of production of beta globin. Patients homozygous or doubly heterozygous for beta (0) thalassemic genes cannot make normal beta chains and are therefore unable to make any hemoglobin A.

Beta (+) thalassemia — Beta (+) thalassemia refers to mutations that result in decreased production of beta globin. Patients homozygous for beta (+) thalassemic genes are able to make some hemoglobin A, and are generally less severely affected than those homozygous for beta (0) genes.

Beta thalassemia major — Beta thalassemia major is the term applied to patients who have either no effective production (as in homozygous beta (0) thalassemia) or severely limited production of beta globin. These are the patients originally described by Cooley (Cooley's anemia). Starting during the first year of life, they have profound and life-long transfusion-dependent anemia.

Beta thalassemia minor — Beta thalassemia minor (beta thalassemia trait) is the term applied to heterozygotes who have inherited a single gene leading to reduced beta globin production. Such patients are asymptomatic, may be only mildly anemic, and are usually discovered when a blood count has been obtained for other reasons.

Beta thalassemia intermedia — Beta thalassemia intermedia is the term applied to patients with disease of intermediate severity, such as those who are compound heterozygotes of two thalassemic variants (table 1). These patients have a later clinical onset and a milder degree of anemia, which may or may not require transfusional support.

STAGES OF INCREASED ICP

Stages of intracranial hypertension

Minimal increases in ICP due to compensatory mechanisms is known as stage 1 of intracranial hypertension.

When the lesion volume continues to increase beyond the point of compensation, the ICP has no other resource, but to increase. Any change in volume greater than 100–120 mL would mean a drastic increase in ICP. This is stage 2 of intracranial hypertension.

Characteristics of stage 2 of intracranial hypertension include compromise of neuronal oxygenation and systemic arteriolar vasoconstriction to increase MAP and CPP.

Stage 3 intracranial hypertension is characterised by a sustained increased ICP, with dramatic changes in ICP with small changes in volume.

In stage 3, as the ICP approaches the MAP, it becomes more and more difficult to squeeze blood into the intracranial space. The body’s response to a decrease in CPP is to raise blood pressure and dilate blood vessels in the brain. This results in increased cerebral blood volume, which increases ICP, lowering CPP and perpetuating this vicious cycle.

This results in widespread reduction in cerebral flow and perfusion, eventually leading to ischemia and brain infarction.

Neurologic changes seen in increased ICP are mostly due to hypoxia and hypercapnea and are as follows:

1. Decreased level of consciousness (LOC),

2. Cheyne–Stokes respiration,

3. Hyperventilation,

4. Sluggish dilated pupils and

5. Widened pulse pressure.

Blood Transfusion

Transfusion Technique:

- Maximum time over which blood products can be administered is 4 hrs for 1 unit because of danger of bacterial proliferation & RBC hemolysis;

- If slower infusion rate is required, half of the unit may be infused while other portion remains refrigerated in the blood bank;

- If flow rate is interrupted for >30 minutes, unit must be discarded;

- Blood should be administered through 170 um filters to prevent infusion of macro-aggregates of fibrin and debris as well as leukocytes; 

- Patients should be observed for the first 5-10 min of a transfusion and then examined frequently for signs of fluid overload and other adverse reactions;

- Emergent transfusion:

- In most cases an Rh type and screen takes 10 minutes and is safer than using O negative blood;

- Characteristics of pRBC;

    - approx 300 +/- 25 mL

   

 - hematocrit: 70 +/- 5%;

 - one unit of pRBCs should increase hemoglobin by approximately 1 gm/dl;

 - citrate is used as an anticoagulant in blood products during plasmapheresis;

    

- citrate is converted to bicarb by liver & causes metabolic alkalosis

- induction of a metabolic alkalosis may produce an abrupt increase in the  hemoglobinn oxygen affinity;

- w/ transfusion actual amount of potassium administered is approx between 5.2 to  6.6 mEq per unit of pRBC;

- since the mean age of blood administered to trauma pts is 13.5 days (and not 35 to  49 days - expiration date of blood), the actual amount of potassium administered per  unit may be only 1 to 3 mEq;

- w/ massive transfusion hypokalemia is more frequently encountered than  hyperkalemia;- this may be also due to alkalosis (from citrate)

- DPG:

- w/ blood that is stored in acid citrate dextrose (ACD) solution for upto to three  weeks is based on the survival of at least 70% of cells in recipients circulation;

- during 3 week period, there is decline in  2-3 disphosphoglycerate (DPG) and a  progressive increase in hemoglobin oxygen affinity (left shift of the oxygen   dissociation curve);

- after transfusion DPG levels require 24 hours or longer to return nl;

- Citrate toxicity:

- can be prevented or its effects minimized by the administration of Ca;

- historically 1gm of CaCl has been given for every four units of blood administered until such time as the pt is normothermic, euvolemic, and is known to have reasonably normal hepatic function;

- if Ca gluconate is used, dose must be 4 times greater than w/ CaCl;

- improved approach is to measure the ionized calcium level.

Complications of Blood Transfusion:

- Blood Product Menu:

- pRBCs - Fresh Frozen Plasma - Platlets - Cryoprecipitate - Transfusion Therapy - Coag Pathway

- Acidemia and Hyperkalemia: from massive transfusions;

- massive transfusion: transfusion of pRBC >6-8 units, must also provide platlets;

            - 8 units platlets for ea 10-12 units pRBC's transfused;

            - 2 units of FFP

            - Ca replacement if hypocalcemic (2nd to citrate)

            - references:

                   

- Electrolyte and acid-base disturbances caused by blood transfusions.

- Hyperkalemia after packed red blood cell transfusion in trauma patients.

- Post-Transfusion Alkalosis:

           - the early net result of successful resuscitation is post-transfusion alkalosis in 

            the patient;

           - the sodium citrate is converted to bicarbonate

           - the alkalosis is associated with increased potassium excretion;

- Hypocalcemia:

           - some recommend calcium supplementation for patients receiving greater 

            than 100 ml/min;

           - give 0.2 gm of CaCl in a separate line for each 500 ml given;

           - some believe that most patients will tolerate 1 unit pRBC q 5 min without 

             requiring calcium supplementation;

- Hemolysis:

    - Non hemolytic reaction:     

           - typically, this reaction occurs after a significant portion of the blood has 

            already been transfused;

           - note: hives + hypotension = anaphylaxis

           - management:

                  - by itself, may continue the transfusion (benadryl 50mg PO/IV);

                  - prior to future transfusions, the patient should be pre-medicated 

                   w/ benadryl 50mg PO/IV (not IM);

                  - if this fails to prevent urticarial rxn, washed RBC's should be

                   given;

                  - w/ mild febrile transfusion reactions fever w/o evidence of 

                   hemolysis or more severe symptoms), antipyretics can be used;

    - Acute hemolytic reaction:

           - most severe and potentially dangerous transfusion reactions;

           - acute intravascular hemolysis occurs during or shortly after transfusion of 

            incompatible blood and is usually due to preformed antibodies; 

                  - typically this reaction occurs early w/ as little as 30 cc of 

                   transfused blood;

           - Manifestations:  

                  - fever, chills, back or chest pain, N/V, and evidence of 

                    hemodynamic instability;

           - Required labs:

                  - spin a hematocrit to look for a pink plasma layer indicates 

                    hemolysis;

                  - pink-red (spun) plasma indicates that greater than 20 mg/dl of 

                   free hemoglobin is present;

                  - send off a DIC screen: PT/PTT, fibrinogen, fibrinogen

                   degradation products, serum bilirubin;

                  - culture of the patient and the donor blood is indicated if there is 

                    suspicion of bacterial contamination;

                  - repeat cross match;

                  - Coomb's Test, Free Hb;

                  - CBC, RBC morphology;

                  - send Donor's Blood back to the blood back;

                  - repeat cross match;

           - Management:

                  - try to preserve intravascular volume and protect against acute

                   renal failure;

                         - NS 500 ml IV "wide open"

                  - monitor the urine output closely and maintain a brisk diuresis 

                   (greater than 100 ml/hr);

                  - consider alkalinization of the urine with bicarbonate (1 mEq/kg 

                   IV until urine pH =7.5-9.0)

                         - will facilitate the excretion of free hemoglobin 

           - Reference:

                  - Extracorporeal hemolysis in orthopedic patients. Report of two 

                   cases.

- Transmission of disease:

- Increased infection rate:

- septic reaction: considered when high fever and hypotension accompany a 

 transfusion reaction;

Immunostimulant for treatment of Malignant melanoma ?

Immunostimulant for treatment of Malignant melanoma ?

A) Levamisol

B) BCG

C) Aldesleukin

D) Methotrexate

Ans: ?C (Aldesleukin)

Used as an adjunct in metastatic renal cell carcinoma, recently approved for Tx of metastatic melanoma.

Aldesleukin toxicity:

Treatment associated w/ serious cardiovascular toxicity resulting from capillary leak syndrome

involves loss of vascular tone, leakage of plasma proteins, adn fluid into extravascular space

may result in hypotension, reduced organ perfusion and even death.

A. Levamisole: 

Antiparasitic drug that stimulates maturation/ proliferation of T cells, enhances T- cell mediated immune responses.

Adjunctive treatment together w/ 5-FU and leucovorin after surgical resection in patients w/ dukes stage C colon cancer.

Has been used in treatment of nephrotic syndome.

Adverse effects: neutorpenia, anemia, thrombocytopenia, agranulocytosis, encephalopathy assoc. w/ demyelination.

B. BCG: 

Bacillus-calmette-guerin used as a non specific immunostimulant.

Used for intravesical therapy of bladder cancer.

D. Methotrexate 

It is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid.

Interferons beta 1a, Iinterferon beta 1b:

Approved for use in MS

Interferons gamma B

Used in chronic granulomatous disease, activates phagocytes.

Oprelvekin:

Recombinant form of human IL 11 derived from genetically altered E. coli, stimulates platelet formation.

Used to treat thrombocytopenia.

Filgrastim:

Granulocyte colony stimulating factor- a 175 aminoacid glycoprotein produced by e. coli, stimulates CFU-G to increase neutrophil prodution. It is a recombinant, many valency, polypeptide. Lineage-specific hematopoietic agent, works on one cell line, stimulates peripehral blood stem cells.

Used to stimulate bone marrow recovery during cancer chemotherapy.

Sargramostim:

Derived from yeast, nonlineage specific hematopoetic agent as it stimulates both granulocytic and macrophage progenitor cells and the mature cells. Receptors on these cells to which sargramostim binds

similar to endogenous cytokine GM-CSF differing only in one amino acid.

Promotes myeloid recovery in patients given high dose chemotherapy for:

-Non-hodgkins lymphoma

-Acute lymphoblastic leukemia

-Hodgkins disease patients who are undergoing bone marrow transplantation

-Used to promote myeloid recovery after standard dose chemotherapy

-Used to help myeloid recovery after BMT

-To treat neutropenia associated w/ AIDS.

Dose related effects:

May be difficult to separate effects due to endogenous GM-CSF and exogenous Sargramostim.

High doses assoc. w/ bone pain, flu-like symptoms, fever, diarrhea, N and V, rash.

* contraindicated in patients w/ heart failure, pulmonary edema, and yeast hypersensitivity.

Epoetin- alpha (erythropoetin):

Recombinant human growth factor responsible for stimulating comitted erythroid precursors resulting in erythropoesis.

Recominent erythropoietin therapy in conjunction w/ adequate iron intake is used in the treatment w/ anemia assoc w/ :

-Surgery

-Treatment w/ zidovudine-induced anemia in AIDs patients

-Cancer chemotherapy (myelosuppressive agents, when chemotherapeutic agents are highly nephrotoxic they may cause anemia)

-Prematurity

-Treatment w/ anemia assoc. w/ chronic renal disease including renal failure.

Thrombopoetin:

Myeloid cytokine growth factor is distinct from but analogous to erythropoietin, G-CSF and GM-CSF

cloning and expression of recombinant human thrombopoietin as a fusion protein combining GM-CSF and 

IL 3 has been very important for patients whose boen marrow has been compromised by chemo

selectively stimulates megakaryocytopoiesis.

Recombinant fusion protein-thrombopoetin + GM-CSF + IL 3 is used to treat anemia, neutropenia, and thrombocytopenia assoc. w/ high dose chemo.

Recombinant human thrombopoetin is used in accelerating platelet recovery in patients undergoing hematopoetic stem cell transplantation.

RA TREATMENT IN PREGNANCY

Methotrexate should be avoided in women trying to conceive or who are pregnant since it is a proven teratogen (pregnancy category X). The data on biologics during pregnancy is much less clear. 

The anti-TNF therapies are all pregnancy category B. 
The other commonly used biologics in RA (abatacept, rituximab, tocilizumab) are pregnancy category C. The Food and Drug Administration (FDA) currently warns against using biologics in pregnancy. 

For women, who require therapy during pregnancy, glucocorticoids, hydroxychloroquine, and occasionally azathioprine (after the first trimester) are the preferred therapies for most physicians who have experience prescribing these agents during pregnancy.

Methotrexate is to be avoided, in particular, since it is a proven teratogen (pregnancy category X). It should be stopped for at least 1 menstrual cycle and as much as 6 months prior to attempting to conceive. 

Men with RA on methotrexate should also discontinue methotrexate for 3 months or more prior to conception. 

The data on biologics during pregnancy are much less clear. There have been case series describing various congenital anomalies affecting fetuses of women using these agents, and there have also been anecdotal reports of women experiencing normal pregnancies and good fetal outcomes with exposure to these compounds. 

The anti-TNF therapies are all pregnancy category B (animal reproduction studies have failed to demonstrate a risk to the fetus, and there are no adequate and well-controlled studies in pregnant women; or animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester). 

The other commonly used biologics for RA (abatacept, rituximab, tocilizumab) are pregnancy category C (animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks).

VIT-D

The Vitamin That's Not a Vitamin

The fourth vitamin to be discovered, vitamin D is a group of secosteroid compounds that include ergocalciferol (vitamin D₂) and cholecalciferol (vitamin D₃). The term "vitamin" is generally reserved for vital substances the body cannot synthesize on its own. Given cholesterol and sunshine, the body can synthesize its own vitamin D, so it's not technically an essential dietary vitamin.

Serious deficiencies in vitamin D can lead to rickets, and it was research into this childhood disease, the pediatric form of osteomalacia, that led to the vitamin's 1922 discovery by Edward Mellanby.

Vitamin D and Bone

Vitamin D has long been known to play an important role in bone health, and several recent studies provided additional confirmation. One study suggested that low levels of vitamin D increase the risk for forearm fracture in children, and another showed that girls who consumed the most vitamin D had the lowest risk for stress fractures. It's not just children who are at risk: 44% of postmenopausal women treated for distal radius fracture were vitamin D deficient or insufficient. And a meta-analysis showed that high doses of vitamin D lower the risk for fracture by 14% to 30% in people age 65 years or older. 

Vitamin D and Respiratory Infections?

If Linus Pauling were alive today, perhaps he would turn his attention away from vitamin C and write "Vitamin D and the Common Cold."

One randomized controlled trial suggested that vitamin D supplementation reduced acute respiratory tract infections in children during the long, cold, and dark Mongolian winter. Another randomized controlled trial showed that vitamin D reduced symptoms and antibiotic use in a group of patients with an increased frequency of respiratory infections. On the other hand, a third randomized controlled trial showed no effect of vitamin D on reducing the incidence or severity of respiratory infection in healthy adults.

Links to Diabetes

Low levels of vitamin D have been linked to several types of diabetes. A study conducted in Australia found that children with type1 diabetes are more likely to have low levels of vitamin D. It's unclear, however, whether low levels of vitamin D caused the diabetes or vice versa. A larger study,  in active-duty military personnel in the United States, found that those with low levels of vitamin D were more likely to develop insulin-requiring diabetes within 1 year. And women who have low vitamin D levels during their first trimester of pregnancy were more likely to develop gestational diabetes.

Vitamin D and Cardiovascular Disease

Numerous epidemiologic studies, including the largest one to date, suggest that a low vitamin D level increases the risk for cardiovascular disease. But there may be a threshold effect, with heart health improving as circulating vitamin D levels increase from 20 to 60 nmol/L, followed by a plateau or perhaps even an increase in risk at higher levels. Unfortunately, a randomized controlled trial among older women failed to find evidence that vitamin D supplementation improved markers of heart health

Obesity

Women with low levels of vitamin D during pregnancy may have children that are more prone to excess body fat at age 6 years. Furthermore, children ages 6 to 18 years who are overweight are more likely to have low vitamin D levels. Adequate levels of vitamin D are associated with less weight gain among women age 65 and olde

Vitamin D and Cancer

Less information has been published about connections between vitamin D and cancer, but some developments have occurred in the past year. In a result the researchers termed "unexpected," women with breast cancer who were being treated with zoledronic acid for bone complications had a lower risk for bone recurrence if they had sufficient vitamin D levels. Vitamin D supplementation may help breast cancer survivors adhere to adjuvant treatment with aromatase inhibitors. And differences in vitamin D–related genes may contribute to increased susceptibility to colon cancer among black Americans.

Neurologic Function

Vitamin D has been tied to several higher neurologic functions. Studies have linked autism to low vitamin D during pregnancy, a connection that was strengthened by a map showing that autism rates were highest among children living in states with the lowest levels of ultraviolet B radiation. People with Alzheimer's disease tend to have low levels of vitamin D, and better cognitive test results are linked to higher vitamin D levels. Vitamin D₃may help clear the brain of amyloid-β. And low vitamin D levels in pregnant women have been associated with poor language development in their offspring.

Stroke and Multiple Sclerosis

Data from the Honolulu Heart Program show that people with low dietary vitamin D at baseline were about 25% more likely to sustain thromboembolic stroke, but not hemorrhagic stroke, during the ensuing 34 years.

The last year has seen a flurry of studies linking vitamin D to multiple sclerosis (MS), and all of them tie low levels of vitamin D to the disease. Three of these studies were published in a single issue of the journal Neurology. Another study linked low levels of vitamin D plus exposure to the Epstein-Barr virus to the development of MS. Low vitamin D levels predict a near-term conversion of clinically isolated syndromes to definite MS. And the risk of developing MS has been linked to lower sun exposure in early life.

Pain

About half of women prescribed aromatase inhibitors for metastatic breast cancer suffer intense musculoskeletal pain, but high-dose vitamin D₂ supplements appear to help. A single oral dose of 300,000 IU of vitamin D appears to help with dysmenorrhea. And a low level of vitamin D in black Americans increases the risk for knee osteoarthritis pain.

Lung Disorders

High-dose vitamin D may speed tuberculosis recovery. And low vitamin D levels appear to be linked to the need for steroids in asthma and may also blunt the effectiveness of asthma treatment.

For chronic obstructive pulmonary disease, however, the story isn't as clear cut. According to one study, high-dose vitamin D supplementation improves exercise capacity and respiratory muscle strength during rehabilitation. But according to another, high-dose supplements failed to prevent exacerbations or secondary outcomes.

Gastrointestinal Disorders

Women with sufficient vitamin D levels at baseline are 62% less likely to develop Crohn's disease over 22 years than those with vitamin D insufficiency.

Women living at southern latitudes in the United States are 52% less likely to have inflammatory bowel disease than those living in the north

Kidney Disease

Vitamin D deficiency is almost universal among patients with chronic kidney disease (CKD). Two recent studies independently concluded that high-dose cholecalciferol (vitamin D₃) supplementation safely prevents and corrects this in patients undergoing dialysis. Vitamin D supplementation also lowers hepcidin levels in patients with CKD

Within the past year, studies have shown that vitamin D may reduce risk for dental caries, low vitamin D may be a result of depression.  vitamin D deficiency increases risk for perforated eardrums, and low vitamin D is linked to food allergy. And the list goes on.

How Much Is Enough?

There's little consensus about what blood levels of vitamin D are adequate, and even less on how much supplementation is enough. The Institute of Medicine says blood levels should be 20 ng/mL, but the Endocrine Society sets the level at 30 ng/mL. The US Recommended Dietary Allowance is 600 IU for people ages 1 to 70 years and 800 IU for those who are older. Some authorities recommend that people who are deficient should receive supplements of 1000 to 2000 IU daily, but others have recommended single-bolus doses of up to 500,000 IU.

How to Measure?

If there's little agreement on how much vitamin D we need, there's even less on how to measure blood levels. You can choose an old, slow, but accurate method, or you can choose one of several new and fast but wildly inaccurate methods. According to one study, these rapid tests may be inaccurate as much as 40% of the time, most often characterizing patients as vitamin D deficient when they're not

Elixir of Life?

While vitamin D appears to be involved in almost every body system, some researchers are looking at the big picture — overall mortality. Oral active vitamin D is associated with reduced all-cause mortality in patients undergoing peritoneal dialysis. Vitamin D has also been linked to lower mortality in patients with pneumonia. And a large meta-analysis found that increased intake of vitamin D plus calcium, but not vitamin D alone, is linked to a decrease in all-cause mortality among elderly patients

And Now for Something Completely Different

A recent study suggests that some people with a genetic predisposition to longevity have a reduced frequency of a gene variant that predisposes people to high vitamin D levels. They also have lower levels of vitamin D. If only science gave us simple, unambiguous answers!

Vitamin D and Bone

Low Vitamin D Linked to Forearm Fracture Risk in Children

Lower Stress Fracture Risk in Girls Linked to Vitamin D Intake

Nearly Half of Older Women With Arm Fractures Have Low Vitamin D

High Vitamin D Doses Lower Fracture Risk for Most Vulnerable

Vitamin D and Respiratory Infections

Vitamin D Supplementation Cuts Respiratory Infections

Vitamin D May Reduce Respiratory Infection Symptoms

Vitamin D Ineffective for Respiratory Tract Infections

Vitamin D and Diabetes

Lower Vitamin D Levels Linked to Type 1 Diabetes

Diabetes Risk Linked to Low Vitamin D Levels

Low First-Trimester Vitamin D Predicts Gestational Diabetes

Vitamin D and Cardiovascular Disease

Largest Epidemiologic Study to Date Links Low Vitamin D to CVD Risk

New Meta-Analysis Suggests 'Threshold' Effect for Vitamin D and CVD

Vitamin D Supplements May Not Improve Heart Health

Vitamin D and Obesity

Low Maternal Vitamin D May Lead to Higher Body Fat in Kids

Overweight Kids More Likely to Be Deficient in Vitamin D

Vitamin D Linked to Modest Decrease in Weight Gain

Vitamin D and Cancer

Vitamin D: 'Surprise' Prognostic Marker in Breast Cancer

Vitamin D May Help Breast Cancer Survivors Stay on Track





Vitamin D and Neurologic Function

More Evidence Vitamin D May Reduce Autism Risk

Low Vitamin D Linked to Alzheimer's Disease

Studies Show How Vitamin D3 Helps Clear Amyloid in AD

Prenatal Vitamin D May Influence Kids' Language Skills

Vitamin D and Stroke/Multiple Sclerosis

Low Vitamin D in Diet Linked to Increased Stroke

Vitamin D Linked to Disease Activity in MS

Low Vitamin D, Epstein-Barr, Linked to Later MS

MS Risk Linked to Low Sun Exposure Early in Life

Vitamin D and Pain

Vitamin D Improves Pain From Aromatase Inhibitors

Can Vitamin D Treat Pain?

Osteoarthritis Knee Pain Linked to Vitamin D, Race



Vitamin D and Lung Disorders

High-Dose Vitamin D May Speed Recovery From Tuberculosis

Low Vitamin D Linked to High IgE, Need for Steroids in Asthma

Low Vitamin D May Blunt Effectiveness of Asthma Treatment

Vitamin D Supplementation Boosts COPD Rehabilitation

High-Dose Vitamin D Fails to Mitigate COPD Exacerbations

Vitamin D and Gastrointestinal Disorders

Vitamin D May Decrease Risk for Crohn's Disease

Less Inflammatory Bowel Disease Seen in Southern Latitudes

Vitamin D and Kidney Disease

Vitamin D Deficiency Likely Among Many Patients Starting Dialysis

High-Dose Cholecalciferol Prevents Vitamin D Insufficiency in Kidney Disease

Vitamin D Deficiency Safely Corrected in Dialysis Patients

Vitamin D Lowers Hepcidin Levels in CKD Patients



Vitamin D and Other Disorders

Vitamin D Supplements May Reduce Risk for Dental Caries

Low Vitamin D a Result, Not a Cause, of Depression

Vitamin D Deficiency Linked With Eardrum Perforation Risk

Infant Food Allergy Linked to Low Vitamin D

How Much Is Enough, and How Best to Measure Blood Levels?

Vitamin D Consensus Remains Elusive Despite Recommendations

Sun Exposure Not Enough to Correct Vitamin D Deficiency

Newer Vitamin D Tests Often Inaccurate: Study

Vitamin D and Overall Mortality

Patients on Peritoneal Dialysis May Benefit From Vitamin D

Vitamin D Levels Linked to Mortality in Patients With Pneumonia

Vitamin D With Calcium May Reduce Mortality in Elderly

Low Vitamin D Levels Linked to Longer Life

COPD-Guidelines-2

According to ACP/ACCP/ATS/ERS, when to use combination therapy instead of monotherapy has not been clearly established. The evidence is insufficient to support a strong recommendation for the broad use of combination therapy, and clinicians should weigh its potential benefits and harms on a case-by-case basis. Taking this into consideration, the guideline suggests that clinicians may administer combination inhaled therapies (LAAC, LABA, or ICS) for symptomatic patients with stable COPD and FEV₁ < 60% predicted.

GOLD recommends against regular use of antitussives, immunoregulators, mucolytic agents, antioxidant agents, AAT augmentation therapy (for COPD that is unrelated to AAT deficiency), and vasodilators. GOLD is the only guideline developer to address phosphodiesterase-4 inhibitors, specifically roflumilast. According to GOLD, roflumilast can reduce exacerbations treated with oral or systemic glucocorticosteroids, and these effects are seen when it is added to long-acting bronchodilators. Note that ACP/ACCP/ATS/ERS provided no guidance in this area.

Other points made in recommendations:

GOLD also says that treatment for very severe COPD can be administered in 3 ways: long-term continuous therapy, during exercise, and to relieve acute dyspnea. 

UMHS points out that in patients with very severe COPD, long-term oxygen therapy has been shown to improve the following outcomes:

• Mortality
• Quality of life
• Cardiovascular morbidity (ie, pulmonary hypertension)
• Depression
• Cognitive function
• Exercise capacity
• Frequency of hospitalization

Virtually no adverse effects occur with long-term oxygen therapy.

Appropriate patient education topics cited by GOLD and UMHS include: information about the nature of COPD, including pathophysiology, triggers, and risk factors; smoking cessation; advance directives and end-of-life decisions; exacerbation recognition and self-management; strategies to help minimize dyspnea; and appropriate usage of inhalers, oxygen, and medications.

GOLD describes bullectomy as an older surgical procedure for bullous emphysema. Removal of a large bulla that does not contribute to gas exchange decompresses the adjacent lung parenchyma. Bullectomy can be performed thoracoscopically. In carefully selected patients, this procedure is effective in reducing dyspnea and improving lung function. Note: ACP/ACCP/ATS/ERS did not provide guidelines for surgery.

GOLD notes that in appropriately selected patients with very advanced COPD, transplantation has been shown to improve quality of life and functional capacity. UMHS adds that consideration of transplantation potential requires comanagement with a pulmonary specialist for detailed assessment of baseline pulmonary physiology and potential contraindications.

ACP/ACCP/ATS/ERS did not provide guidelines for surgery.