Bronchial asthma is a heterogenous disease characterized by airway inflammation and hyperresponsiveness. It is defined by symptoms like dyspnea, cough, wheeze and chest tightness that vary in intensity. Risk factors include atopy, genetic predisposition, gender, obesity, infections, allergens, occupational sensitizers, smoking, exercise and certain foods, drugs and environmental factors. Pathophysiology involves airway inflammation mediated by type 2 helper T cells and eosinophils. Treatment involves bronchodilators like beta-2 agonists for symptom relief and inhaled corticosteroids to control underlying inflammation.
ASTHMA etiology, risk factors, pathophysiology and it's managementPoovarasanA5
Asthma is a common disease which we come across all over the world, certain factors helps to avoid and try to improve livelihood by changing life style modifications
ASTHMA etiology, risk factors, pathophysiology and it's managementPoovarasanA5
Asthma is a common disease which we come across all over the world, certain factors helps to avoid and try to improve livelihood by changing life style modifications
pharmacothrapy of asthma.pptxBronchial asthma is a chronic respiratory diseas...AbhishekKumarGupta86
pharmacotherpy of asthma M pharm 2nd sem.
Bronchial asthma is a chronic respiratory disease characterized by inflammation and narrowing of airways in the lungs, which cause difficulty in breathing.
Symptoms can include coughing, wheezing, shortness of breath and chest tightness. These symptoms can be mild or severe and can come and go over time.
Although asthma can be a serious condition, it can be managed with the right treatment.
Asthma affected an estimated 262 million people in 2019 (1) and caused 455 000 deaths.
Bronchial asthma for pharnacy student.pptxmekulecture
Under normal conditions, only approximately 1 mL of the 125 mL of glomerular filtrate that is formed each minute is excreted in the urine.
The other 124 mL is reabsorbed in the tubules.
This means that the average output of urine is approximately 60 mL/hour… approximately 1.5L urine per day.
pharmacothrapy of asthma.pptxBronchial asthma is a chronic respiratory diseas...AbhishekKumarGupta86
pharmacotherpy of asthma M pharm 2nd sem.
Bronchial asthma is a chronic respiratory disease characterized by inflammation and narrowing of airways in the lungs, which cause difficulty in breathing.
Symptoms can include coughing, wheezing, shortness of breath and chest tightness. These symptoms can be mild or severe and can come and go over time.
Although asthma can be a serious condition, it can be managed with the right treatment.
Asthma affected an estimated 262 million people in 2019 (1) and caused 455 000 deaths.
Bronchial asthma for pharnacy student.pptxmekulecture
Under normal conditions, only approximately 1 mL of the 125 mL of glomerular filtrate that is formed each minute is excreted in the urine.
The other 124 mL is reabsorbed in the tubules.
This means that the average output of urine is approximately 60 mL/hour… approximately 1.5L urine per day.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
2. INTRODUCTION
• Asthma is a heterogenous disease characterised by airway
inflammation and hyperresponsiveness.
• It is defined by history of dyspnoea, cough, wheeze and chest
tightness which vary over time and in intensity.
3. RISK FACTORS AND TRIGGERS
ENDOGENOUS FACTORS
Atopy Genetic
predisposition
Gender Obesity Infections
• Major risk factor
• Genetic
predisposition to
develop allergic
reactions.
Ex: Allergic rhinitis,
allergic dermatitis.
• Seen with
polymorphism of
genes on ch 5q
• Epigenetic
mechanism like
DNA methylation
and histone
modification in
fetus.
• Two times more
common in males
than females till
childhood
* Due to increased
proinflammatory
adipokines
• Rhinovirus
• RSV
• Coronavirus
• Mycoplasma
4. RISK FACTORS AND TRIGGERS
ENVIRONMENTAL FACTORS
Indoor allergens Outdoor allergens Occupational
sensitizers
Ventilation Smoking
• Most common –
dermatophagoides
-house dust mite
• Domestic pets
• NO2 from
cooking stoves
• NO2
• SO2
• Diesel
particulates
• Pollen, fungal
spores
• Animal allergens
in lab workers
• Chemicals
• Aerosols
• Dampness and
poor ventilation
• Active and passive
smoking
5. • Exercise causes increase osmolality of airway lining which
stimulates the mast cells
• Cold air
• Drugs – Beta blockers, Aspirin and rarely ACE inhibitors
• Stress
• Food – Shell fish, meta bisulphite, tartrazine
• GERD
RISK FACTORS AND TRIGGERS
TRIGGERS
6. PHENOTYPES OF ASTHMA
Intrinsic / Idiosyncratic asthma Extrinsic asthma
Triggered by viral or bacterial infection Atopy related.
Ex: Dermatophagoides
S.IgE normal S.IgE elevated
Skin test negative Skin test positive
7. • Type 2 inflammation is associated with eosinophilia and increased
FeNO. It is seen in 50% bronchial asthmatics with severe asthma.
Cytokines involved are IL4, IL5, IL13. This responds to corticosteroids.
• Non Type 2 inflammation is associated with neutrophilia. It doesn’t
respond to corticosteroids
• Brittle asthma
- Type 1 is associated with frequent fluctuations in lung function with
exacerbation. It’s treated with high dose ICS, LABA, oral steroids.
- Type 2 is associated with near normal lung function followed by
sudden decline and death of the patient due to airway anaphylaxis. It’s
treated with inj adrenaline.
9. • Cytokines: Th2 cell produce IL4, IL5, IL9, IL13 which mediate the
allergic reaction. Proinflammatory cytokine TNF alpha and IL-1 beta
amplify the response. TSLP(Thymus Stimulated Lymphopoietin) is
released from epithelial cell and increases release of chemokines from
dendritic cell.
• Chemokines: Eotaxin (CCL11) attracts eosinophils via CCR3 whereas
CCL17 and CCL22 attract Th2 cells via CCR4.
• Airway Remodelling: It refers to characteristic structural changes
in bronchial asthma. Epithelial damage results in loss of barrier
function and allows penetration of allergens and exposure of the sensory
nerves which may lead to reflex neural affects on the airway.
10. • Basement membrane is thickened due to sub-epithelial fibrosis with the
deposition of Type 3 and 5 collagen. There is also hypertrophy and
hyperplasia of the smooth muscle due to PDGF. Angiogenesis is seen
due to VEGF. Microvascular leakage from post capillary venules results
in airway edema. Increased mucous secretion due to hyperplasia of
goblet cells and submucosal glands occurs.
11. ASPIRIN INDUCED ASTHMA
• Seen only in 1-5 % of asthmatics. It is preceded by perennial rhinitis and
nasal polyps. Aspirin intake causes rhinorrhoea, conjunctival injection,
facial flushing and wheezing
LOX pathway
COX pathway
Leukotrienes
Prostaglandins
Aspirin
Archidonic Acid
12. • It is due to the increase in the leukotrienes LT C4, LT D4, LT E4
• Treatment : Inhalational corticosteroids, SABA, Antileukotrienes.
ASPIRIN INDUCED ASTHMA
13. CLINICAL FEATURES
SYMPTOMS
• Wheeze, dyspnoea, cough, chest tightness.
• Nocturnal worsening and typical awakening in early morning hours.
• Prodromal symptoms like itching under the skin, discomfort
between the scapulae, inexplicable fear(impending doom) may be
seen.
• Seasonal variation, symptoms more common during winters
14. • Expiratory wheeze, rhonchi throughout the chest.
• Hyper inflation
• Children may present with non productive cough(cough variant asthma)
INVESTIGATIONS
• Chest X-ray: It shows hyper inflated lungs.
• Spirometry is considered to be the gold standard for diagnosis of asthma
CLINICAL FEATURES
SIGNS
15. SPIROMETRY: FEV1/FVC RATIO <0.7 indicates obstructive pattern
POSITIVE BRONCHODILATOR REVERSIBILITY
IS DIAGNOSTIC OF ASTHMA
Administraton of 400mcg Salbutamol ,increases
FEV1>12% OR >200ML,after 15 min duration
POSITIVE BRONCHIAL PROVOCATION TEST:
Useful in patient with no symptoms
Methacholine inhalation causes more than or equal to 20%
fall in FEV1
DIURNAL VARIABILITY >20% Variability of PEFR
POSITIVE EXERCISE CHALLENGE TEST >20% Fall in FEV1
FeNO-Fractional Concentration of Exhaled Nitric Oxide Increased in bronchial asthma with eosinophilia
May not increase in neutrophilic asthma
False positive in atopy,eczema
Skin test Used to identify the allergen.
DIAGNOSIS
16. Fig 2: Spirometry and flow-volume loop in asthmatic compared to normal subject. There is a reduction in
forced expiratory volume in 1 second (FEV1) but less reduction in forced vital capacity (FVC), giving a
reduced FEV1/FVC ratio (<70%).
18. TREATMENT OF BRONCHIAL ASTHMA
• The main drugs for asthma can be divided into bronchodilators, which
give rapid relief of symptoms mainly through relaxation of airway
smooth muscle, and controllers, which inhibit the underlying
inflammatory process.
BRONCHODILATOR THERAPIES
• There are three classes of bronchodilator in current use: β2-adrenergic
agonists, anticholinergics, and theophylline; of these, β2-agonists are
by far the most effective.
19. • β2-agonists :
Mechanism of action: β2-Receptors are coupled through a stimulatory G
protein to adenylyl cyclase, resulting in increased intracellular cyclic
adenosine monophosphate (AMP), which relaxes smooth muscle cells and
inhibits certain inflammatory cells, particularly mast cells.
• Short acting beta agonists: SABA-Albuterol and terbutaline, have a
duration of action of 3–6 h. They have a rapid onset of
bronchodilatation and are, therefore, used as needed for symptom relief
(relievers). Increased use of SABA indicates that asthma is not
controlled. They are also useful in preventing EIA if taken prior to
exercise. SABA are used in high doses by nebulizer or via a metered-dose
inhaler (MDI) with a spacer.
20. • Long-acting β2-agonists (LABA) include salmeterol and formoterol, both of
which have a duration of action over 12 h and are given twice daily by
inhalation
• Ultra Long acting: Indacaterol, olodaterol, and vilanterol, given once daily.
LABA have replaced the regular use of SABA, but LABA should not be given
in the absence of ICS therapy as they do not control the underlying
inflammation. This has led to the widespread use of fixed combination
inhalers that contain a corticosteroid and a LABA, which have proved to be
highly effective in the control of asthma and prevention of exacerbations.
• Example :FORACORT is combination of Formeterol and Budesonide.
21. • SIDE EFFECTS
The most common side effects are muscle tremor and palpitations, which
are seen more commonly in elderly patients. There is a small fall in plasma
potassium due to increased uptake by skeletal muscle cells, but this effect
does not usually cause any clinical problem.
ANTICHOLINERGICS
Mechanism of action:
They prevent cholinergic nerve-induced bronchoconstriction and mucus
secretion. They are less effective than β2-agonists in asthma therapy as
they inhibit only the cholinergic reflex component of bronchoconstriction,
whereas β2-agonists prevent all bronchoconstrictor mechanisms.
22. Short acting muscarinic antagonist(SAMA):Ipratropium Bromide
Long-acting muscarinic antagonists (LAMA): including tiotropium
bromide or glycopyrronium bromide, may be used as an additional
bronchodilator in patients with asthma that is not controlled by maximal
doses of ICS-LABA combinations.High doses of SAMA can
be given by nebulizer in treating acute severe asthma but should only be
given following β2-agonists, as they have a slower onset of
bronchodilation.
Side effects :
The most common side effect is dry mouth; in elderly patients, urinary
retention and glaucoma may also be observed
23. • Theophylline Theophylline use has now fallen out of favor as side effects
are common.
• Mechanism of action:The bronchodilator effect is due to inhibition of
phosphodiesterases in airway smooth-muscle cells, which increases cyclic
AMP. Theophylline activates the key nuclear enzyme histone deacetylase-2
(HDAC2), which is a critical mechanism for switching off activated
inflammatory genes and therefore reduces corticosteroid insensitivity in
severe asthma.
• . It may be used as an additional bronchodilator in severe asthma. Low
doses of theophylline, giving plasma concentrations of 5–10 mg/L, have
additive effects to ICS and are useful in patients with severe asthma. At low
doses, the drug is well tolerated.
24. • IV aminophylline (a soluble salt of theophylline) was used for the treatment of
severe asthma but has now been largely replaced by high doses of inhaled SABA,
which are more effective and have fewer side effects. Aminophylline is occasionally
used (via slow IV infusion) in patients with severe exacerbations that are refractory
to SABA.
• Side Effects. The most common side effects are nausea, vomiting, and headaches
.Diuresis and palpitations may also occur, and at high concentrations cardiac
arrhythmias, epileptic seizures, and death may occur due to adenosine A1-receptor
antagonism. Theophylline side effects are related to plasma concentration and are
rarely observed at plasma concentrations <10 mg/L. Theophylline is metabolized
by CYP450 (CYP1A2) in the liver, and, thus, plasma concentrations may be
elevated by drugs that block CYP450 such as erythromycin and allopurinol
25. CONTROLLER THERAPIES
• Inhaled Corticosteroids ICS are the most effective controllers for
asthma.
• Mode of Action :ICS reduce inflammatory cells ex:Eosinophils in the
airways and sputum, and numbers of activated T lymphocytes and
surface mast cells in the airway mucosa.
• The major effect of corticosteroids is to switch off the transcription
of multiple activated genes that encode inflammatory proteins such as
cytokines, chemokines, adhesion molecules, and inflammatory
enzymes.
26. • Their main mechanism is recruitment of HDAC2, which reverses the
histone acetylation associated with increased gene transcription.
Corticosteroids also activate anti-inflammatory genes such as mitogen-
activated protein (MAP) kinase phosphatase-1, and increase the
expression of β2-receptors.
• They are effective in preventing EIA and nocturnal exacerbations. ICS
are now given as first-line therapy for patients with persistent asthma,
but if they do not control symptoms at low doses, it is usual to add a
LABA as the next step.
27. • Local side effects include hoarseness (dysphonia) and oral candidiasis,
which may be reduced with the use of a large-volume spacer device.
At high doses, there may be some suppression of plasma and urinary
cortisol concentrations
• Systemic Corticosteroids Corticosteroids are used intravenously
(hydrocortisone or methylprednisolone) for the treatment of acute
severe asthma.Approximately 1% of asthma patients may require
maintenance with OCS.
28. • Systemic side effects, including truncal obesity, bruising, osteoporosis,
diabetes, hypertension, gastric ulceration, proximal myopathy,
depression, and cataracts, may be a major problem, and steroid-sparing
therapies may be considered if side effects are a significant problem.
• If patients require maintenance with OCS, it is important to monitor
bone density so that preventive treatment with bisphosphonates or
estrogen in postmenopausal women.
29. Mechanism of action: Cysteinyl-leukotrienes are potent
bronchoconstrictors; they cause microvascular leakage and increase
eosinophilic inflammation
Antileukotrienes, such as montelukast and zafirlukast, block cys-LT1-
receptors and provide modest clinical benefit in asthma.
They are less effective than ICS in controlling asthma but are useful as
an add-on therapy in some patients not controlled with low doses of
ICS, although less effective than a LABA. They are given orally once
or twice daily and are well tolerated.
Antileukotrienes
30. • Cromones Cromolyn sodium and nedocromil sodium are asthma
controller drugs
• Mechanism of action: They inhibit mast cell and effective in blocking
trigger-induced asthma such as EIA and allergen- and sulfur dioxide-
induced symptoms.
• Cromones have relatively little benefit in the long-term control of
asthma due to their short duration of action (at least four times daily
by inhalation
31. • Steroid-Sparing Therapies Methotrexate, cyclosporin A, azathioprine,
gold, and IV gamma globulin have all been used as steroid-sparing
therapies.
• Anti-IgE Omalizumab is a blocking antibody that neutralizes
circulating IgE without binding to cell-bound IgE and, thus, inhibits IgE-
mediated reactions. The treatment is very expensive and is only suitable
for highly selected patients who are not controlled on maximal doses of
inhaler therapy and have a circulating IgE within a specified range.
Omalizumab is usually given as a subcutaneous injection every 2–4 weeks
and appears not to have significant side effects, although anaphylaxis is
very occasionally seen. .
32. NEWER MODALITIES
Anti-IL-5 Antibodies that block IL-5 mepolizumab, reslizumab or its
receptor benralizumab markedly reduce blood and tissue eosinophils and
reduce exacerbations in patients who have persistently increased sputum
eosinophils despite maximal ICS therapy.
Immunotherapy Specific immunotherapy using injected extracts of
pollens or house dust mites has not been very effective in controlling
asthma and may cause anaphylaxis
33. Bronchial Thermoplasty: Bronchial thermoplasty is a bronchoscopic
treatment using thermal energy to ablate airway smooth muscle in
accessible bronchi. It may reduce exacerbations and improve asthma
control in highly selected patients not controlled on maximal inhaler
therapy, particularly when there is no increase in inflammation. .
34. MANAGEMENT OF CHRONIC ASTHMA
• Diagnosis is established by objectively using spirometry or PEF
measurements at home. It is assessed by symptoms, night awakening, need
for reliever inhalers, limitation of activity and lung function.
• There are several validated questionnaires for quantifying asthma control,
such as the Asthma Quality of Life Questionnaire (AQLQ) and Asthma
Control Test (ACT).
36. Parameter Intermittent Mild Persistent Moderate
Persistent
Severe
Persistent
Day time
symptoms
<2/wk >2/wk Daily Throughout the
day
Nocturnal
Symptoms
<2/month >2/month >2/wk Daily
Managemen
t
STEP 1 STEP 2 STEP 3 STEP 4
SABA SABA
+
Low Dose ICS
SABA
+
High Dose ICS
+
LABA
SABA
+
LABA
+
Oral
corticosteroids
37. • Stepwise Therapy: For patients with mild, intermittent asthma, a
SABA is all that is required The treatment of choice for all patients is
an ICS given twice daily.
• It is usual to start with an intermediate dose (e.g., 200 [μg] bid of
[beclomethasone dipropionate] BDP) or equivalent and to decrease
the dose if symptoms are controlled after three months. If symptoms
are not controlled, a LABA should be added, which is most
conveniently given by switching to a combination inhaler.
38. • The dose of controller should be adjusted accordingly, as judged by the
need for a rescue inhaler. Low doses of theophylline or an antileukotriene
may also be considered as an add-on therapy, but these are less effective
than LABA
• If asthma is not controlled despite the maximal recommended dose of
inhaled therapy, it is important to check adherence and inhaler technique.
In these patients, maintenance treatment with an OCS may be needed and
the lowest dose that maintains control should be used.
• Occasionally omalizumab and anti-IL-5 may be tried in steroid-
dependent asthmatics who are not well controlled. Once asthma is
controlled, it is important to slowly decrease therapy in order to find the
optimal dose to control symptoms.
39. Fig 5: Stepwise approach to asthma therapy according to the severity of asthma and ability to
control symptoms. ICS, inhaled corticosteroids; LABA, long-acting β2-agonist; OCS, oral corticosteroid
40. Case history: A 45 yr old female patient presented to the casualty with
chief complaint of dyspnoea,cough and chest tightness,fear of impending
doom since 3 hours. The patient is unable to speak full sentences, highly
uncomfortable, unable to lie down and using accessory muscles for
respiration.
Vitals: BP – 140/90 mm of Hg, PR: 138/min, RR: 30/min, SpO2: 75%
On examination, there is bilateral expiratory wheeze, diffusely present over
the chest.
Patient is a known asthmatic since 10 yrs,not using medications since few
months.
41. Discussion
Acute severe exacerbation of asthma
Clinical features
1.SOB at rest,
2.use of accessory muscles for respiration,
3.RR>30/min,
4.HR>120/min,
5.B/L wheeze diffusely over lungs
6.Pulsus Paradoxus: Fall in B.P. by 12 mm of Hg on inspiration.
Functional criteria: PEFR <50%; Sp02<90%; paO2 <60mm of Hg
42. SILENT CHEST
• Life threatening sign
• On auscultation there is no wheeze, giving a false impression of patient
recovery.
• No sounds are heard due to complete closure of airways .
• Other signs which help in diagnosis are:
1. Altered sensorium
2. Decreased respiratory effort
3. Decreased sPO2,increased Paco2.
43. Treatment of acute exacerbation of asthma
1. Oxygen support
2. Nebulisation with SABA: Salbutamol 5mg by jet every 20min for 3 doses.
Later 2.5-5mg every 1 hr for 4 hrs; SAMA and Inhalational corticosteroids.
3. Systemic Steroids: Injection Hydrocortisone 100mg IV stat
4. If not improving, a trial of IV MgSO4 2gm infusion over 20min can be
given
5. IV Theophylline is useful in acute exacerbation not responding to ICS.
6. In life threatening asthma, patient might need invasive mechanical
ventilation.
44. Differential diagnosis
• In foreign body obstruction, stridor is present .
• In upper airway obstruction, secondary to tumour, stridor and localized
wheeze is present.
• In LVF, bilateral basal crepts, raised JVP, pedal edema are present.
• COPD : Irreversible damage to the airways occurs.
Persistent cough is present and symptoms show less variability.
No Bronchodilator reversibility is seen.
45. ASTHMA COPD OVERLAP
• Few asthmatics who are smokers show features of COPD
• Similarly some patients with COPD show bronchodilator reversibility
and increased airway and blood eosinophils.
• They may benefit from triple therapy with ICS, LABA and LAMA.
46. Refractory Asthma
• A small proportion of patients (~5%) are difficult to control despite
maximal inhaled therapy. It is important to check adherence to therapy
and inhaler technique. Some of these patients will require maintenance
treatment with OCS.
• There are two major patterns of difficult asthma: some patients have
persistent symptoms and poor lung function, despite appropriate
therapy, whereas others may have normal or near normal lung function
but intermittent, severe (sometimes life-threatening) exacerbations.
47. Corticosteroid-Resistant Asthma
• It is defined by a failure to respond to a high dose of oral
prednisone/prednisolone (40 mg once daily over 2 weeks)
TREATMENT
• Low doses of theophylline
• Maintenance treatment with OCS
• Omalizumab- Allergic asthma
• Anti-IL-5 – Mepolizumab, Reslizumab