The Respiratory System (Study Guide)

The respiratory system – UNIT 6 STRUCTURE & FUNCTION Primary function = provides O2 for use by body cells and removes CO2 from blood. Structure upper respiratory tract (nose, nasal cavity, pharynx and larynx) lower respiratory tract (trachea, bronchi and lungs – located in chest cavity) THE UPPER RESPIRATORY TRACT - warms, humidifies and filters air Consists of: 1.Nose and Paranasal sinuses - Provides an airway for respiration - Moistens and warms entering air - Filters and cleans inspired air - Serves as a resonating chamber for speech - Contains the olfactory (smell) receptors 2.External nose 3.Nasal cavity - divided by nasal septum (formed by cartilage) - the nasal cavity is continuous with the nasal portion of the pharynx through the posterior nasal apertures. - the roof of nasal cavity is formed by ethmoid and sphenoid bones of the skull - the floor is formed by the palate which separates nasal cavity from oral cavity below. Anteriorly lies the hard palette and posteriorly lies the soft palette - superior to the nostrils is called nasal vestibule – lined with sebaceous & sweat glands and hair follicles. - The rest of nasal cavity is lined with 2 types of mucous membrane: olfactory mucosa & respiratory mucosa 1. Olfactory mucosa lines the slit-like superior region of nasal cavity and contains smell receptors in its olfactory epithelium. 2. Respiratory mucosa lines most of the nasal cavity. It is richly supplied with seromucous nasal glands contains mucous secreting cells and serous cells that secrete a watery fluid containing enzymes. These glands secrete mucus secreting lysozyme. The mucus traps dust and bacteria, whilst the lysozymes attacks and chemically destroys bacteria. - Respiratory mucosa also secretes defensins (natural antibiotic) that help kill invading microbes. - High water content of mucous film humidifies air. - Ciliated cells create a gentle current that moves the contaminated mucus towards the throat where it is swallowed and digested. - Nasal mucosa is richly supplied with sensory nerve endings so contact with irritating particles triggers a sneeze reflex. - Rich plexuses of capillaries and veins underlie nasal epithelium and warm incoming air. 4. Nasal conchae - Superior, middle & inferior conchae - Curved conchae greatly increases mucosa surface area exposed to air and enhances air turbulence in cavity. - Heavier, non-gaseous particles inhaled in air get trapped. Very few particles larger than 6 μm make it past nasal cavity. 5. Paranasal sinuses - Surrounds nasal cavity - Located in frontal, sphenoid, ethmoid & maxillary bones. - Lightens the skull and helps warm and moisten the air. - The mucus they produce flows into nasal cavity and the suctioning effect by blowing nose help drain the sinuses 6. The Pharynx - aka – the throat - Passageway connecting nasal cavity to larynx and oral cavity to oesophagus - 3 subdivisions: nasopharynx, oropharynx & laryngopharynx - Composed of skeletal muscle Nasopharynx - Serves only as an airway passage. - During swallowing, the soft palate and uvula move upwards to close off the nasopharynx and prevent food from entering nasal cavity. - Contains pharyngeal tonsils or adenoids which traps and destroys pathogens entering nasopharynx. Oropharynx - Lies behind the oral cavity - Extends below soft palate to the epiglottis so both swallowed food and air passes through it - The paired palatine tonsils lie embedded in the lateral walls Laryngopharynx - Connects from oropharynx and serves as a passageway for both food and air -Lies directly above larynx where the respiratory and digestive pathways diverge 7. Larynx - Connects pharynx to trachea. - Voice box - Routes air and food into the proper channels. Prevents food from entering lower respiratory tract. THE LOWER RESPIRATORY TRACT Consists of 2 zones: 1. The respiratory zone – the actual site of gas exchange, composed of bronchioles, alveolar ducts & alveoli 2. The conducting zone – consists of all respiratory passageways from nose to bronchioles. These organs in conducting zone cleanse, humidify and warm incoming air so the air that reaches the lungs has fewer irritants. Epiglottis Elastic cartilage that sits beneath the tongue and in front of the larynx. Its main function is to close over the trachea while you're eating to prevent food entering your airway. Vocal folds two bands of smooth muscle tissue found in the larynx. The vocal cords vibrate and air passes through the cords from the lungs to produce the sound of your voice. Epithelium of larynx Stratifies squamous epithelium lines the top part of larynx – food area. Below vocal cords = pseudostratified ciliated columnar type that filters dust. The power stroke of its cilia moves upwards towards the pharynx to move mucus away from lungs. Voice production Speech involves intermittent release of expired air as the glottis opens and closes. As the length and tension of vocal folds change, the pitch of the sound varies. Greater force = stronger vibrations = louder sound Sphincter functions of the larynx Under certain conditions, the vocal folds act as a sphincter that prevents air passage. During abdominal straining from pooing, the glottis closes to prevent exhalation and the abdominal muscles contract, causing intra-abdominal muscles to rise. This is called Valsalva’s maneuver. Conducting zone structures  Trachea divides to form the right and left bronchi. The right main bronchus is wider, shorter and more vertical then the left – so more common for inhaled foreign objects to get stuck.  Once inside the lungs, each main bronchus subdivides into: Lobar (secondary) bronchi 3 on the right, 2 on the left Bronchioles passages smaller than 1mm diameter Terminal bronchioles passages smaller than 0.55mm diameter As the conducting tubes become smaller, the following structural changes occur: - Support structures change (irregular plates of cartilage replace cartilage rings and by the time bronchioles are reached, the tube walls no longer contain supportive cartilage) - Epithelium type changes (changes from pseudostratified columnar to columnar to cuboidal in terminal bronchioles) - Amount of smooth muscle increases (increases as passageway becomes smaller) Respiratory zone structures  Respiratory bronchioles lead into winding alveolar ducts, which leads into terminal clusters of alveoli – alveolar sacs or alveolar saccules. Type I alveolar cells: -External surfaces of alveoli are densely covered with pulmonary capillaries. -The capillary and alveolar walls and their fused basement membranes form the respiratory membrane – a 0.5 μm blood air barrier that has blood flowing past on one side and gas on the other. Gas exchange readily occurs by simple diffusion across respiratory membrane. Type II alveolar cells: - secretes a fluid containing a detergent-like substance called surfactant that coats the gas-exposed alveolar surfaces. - also secretes antimicrobial proteins – important elements of innate immunity. The pleurae - The pleura includes two thin layers of tissue that protect and cushion the lungs. The inner layer (visceral pleura) wraps around the lungs and is stuck so tightly to the lungs that it cannot be peeled off. The outer layer (parietal pleura) lines the inside of the chest wall. - The pleurae produces pleural fluid which fills the pleural cavity. This lubricating secretion allows the lungs to glide easily over the thorax wall during breathing. The surface tension strongly resists their separation so lungs cling tightly to thorax walls. Conditions: 1. Rhinitis & sinusitis cold viruses, streptococcal bacteria and allergens can cause rhinitis – inflammation of nasal mucosa accompanied by excess mucus production, nasal congestion and postnasal drip. Nasal cavity infections often spread to sinus regions and causes sinusitis (inflamed sinuses) 2. Infected and swollen adenoids Infected and swollen adenoids block air passage in the nasopharynx, causing necessary breathing from mouth. Causes air to be not properly moistened, warmed or filtered before reaching lungs. Chronically enlarged adenoids = both speech & sleep may be disturbed. 3. Laryngitis Inflammation of vocal cords – causes vocal cords to swell, interfering with their vibration. This causes hoarseness or whispering of voice in severe cases. Most often caused by viral infections but also by overusing the voice, very dry air, bacterial infections, tumours on vocal cords or inhalation of irritants. 4. Smoking inhibits and destroys cilia. Without ciliary activity, coughing is the only way to prevent mucus from accumulating in the lungs. Smokers with respiratory congestion should avoid medications that inhibit coughing. 5. Pleurisy inflammation of the pleurae, often results from pneumonia. Inflamed pleurae become rough, resulting in friction and stabbing pain with each breath. As disease progresses, pleurae may produce excessive amounts of fluid. This relieves pain from friction of rubbing together but may exert pressure on the lungs and hinder breathing movements. Fluid accumulation in pleurae = pleural effusion RESPIRATORY PHYSIOLOGY Pressure relationships in thoracic cavity: Intrapulmonary pressure (Ppul) pressure in the alveoli. Intrapulmonary pressure rises and falls with the phases of breathing, but it always equalizes with atmospheric pressure eventually Intrapleural pressure (Pip) pressure in pleural cavity, also fluctuates with breathing phases, but it is always 44mm Hg less than Ppul. Pip = always negative pressure compared to P ul Transpulmonary pressure difference between intrapulmonary and Intrapleural pressure. Ppul  Pip The size of the Transpulmonary pressure determines the size of the lungs at any time. Greater transpulmonary pressure = larger lungs Any condition that equalises Pip with Ppul causes immediate lung collapse! Pulmonary ventilation: Inspiration 1. Diaphragm contracts & flattens 2. External intercostal muscles contract 3. Thoracic cavity volume increases 4. Intrapulmonary volume increases = intrapulmonary pressure decreases 5. Air flows into lungs via pressure gradient (until Ppul = 0) Inspiration ends when Ppul = Patm Expiration 1. Diaphragm relaxes 2. External intercostal muscles relax 3. Thoracic cavity volume decreases 4. Intrapulmonary volume decreases = intrapulmonary pressure increases 5. Air flows out of lungs down pressure gradient (until Ppul = 0) Physical factors influencing pulmonary ventilation: 1. Alveolar surface tension Alveolar film contains surfactant (detergent like complex of lipids and proteins produced by type II alveolar cells). Surfactant decreases the cohesiveness of water molecules so surface tension of alveolar fluid is reduced & less energy needed to overcome forces to expand lungs and discourage alveolar collapse. 2. Lung compliance A measure of the change in lung volume that occurs with a given change in transpulmonary pressure. The higher the lung compliance, the easier is to expand the lungs at any given transpulmonary pressure. CL = VL  (Ppul  Pip) it Lung compliance is determined by 2 factors: o Distensibility of lung tissue o Alveolar surface tension Distensibility is generally high and alveolar surface tension is low in healthy lungs so has high compliance = efficient ventilation Any decrease in the natural resilience of lungs diminishes lung compliance. Lower lung compliance = more energy needed to breathe. Spirometry and lung volumes Measurement TIDAL VOLUME (VT) Typical values 500ml INSPIRATOY RESERVE VOLUME (IRV) Male: 3100ml Female: 1900ml EXPIRATORY RESERVE VOLUME (ERV) Male: 1200ml Female: 700ml Definition Amount of air inhaled/exhaled in one breath Amount of air that can be inhaled with maximum effort above tidal inspiration Amount of air that can be exhaled with maximum effort RESIDUAL VOLUME (RV) Male: 1200ml Female: 1100ml VITAL CAPACITY (VC) Male: 4800ml Female: 3100ml INSPIRATORY CAPACITY (IC) FUNCTIONAL RESIDUAL CAPACITY (FRC) TOTAL LUNG CAPACITY (TLC) Male: 3600ml Female: 2400ml Male: 2400ml Female: 1800ml Male: 6000ml Female: 4200ml above tidal exhalation Amount of air left in the lungs after exhalation with maximum effort: keeps alveoli inflated between breaths Amount of air exhaled with maximum effort after maximum inspiration (VC = VT + IRV + ERV) Maximum amount of air inhaled after a normal exhalation (IC = VT + IRV) Amount of air remaining in lungs after exhalation (FRC = RV + ERV) Maximum amount of air the lungs can hold (TLC = RV + VC) Pulmonary function test Spirometry = useful test for diagnosis of certain lung conditions. It measures ability to inhale and exhale air in relation to time.  Can easily distinguish between obstructive and restrictive pulmonary diseases.  Obstructive diseases TLC, FRC & RV increase because lungs hyper-inflate  Restrictive diseases VC, TLC, FRC & RV decline because lung expansion is limited The main results of spirometry are: 1 FORCED VITAL CAPACITY (FVC) Max amount of air that can be exhaled when a person takes a deep breath and then forcefully exhales as fast as possible. 2 FORCED EXPIRATORY VOLUME (FEV) determines the mount of air exhaled during specific time intervals of the FVC test. FEV in the 1st second (FEV1) is used to classify the severity of obstructive lung diseases. Lung surfactant - Secreted by type II alveolar cells - It is a phospholipid that spreads across alveolar surfaces to reduce surface tension and prevents alveoli from collapsing - Also has bactericidal effect (prevents bacteria growth) Premature babies may have difficulty breathing due to low levels of surfactant Post-natal surfactant therapy used for newborn reparatory distress syndrome (NRDS) Examples of surfactants used in this therapy: beractant & poractant alpha They are administered directly into tracheobronchial tree via an endotracheal tube. Ageing Respiratory performance declines with age, beginning in the mid-20s. General loss of elastic tissue in the lungs increases the likelihood that small airways collapse during expiration and decreases the functional lung volume.  With age the costal cartilages which are connected to the ribs and to the sternum become hardened or calcified.  This causes the chest wall to become more rigid makes it difficult for rib cage to expand and contract during inspiration & expiration = respiratory efficiency decreases ASTHMA   Asthma is a chronic disease characterised by persistent airways inflammation. Asthmatic symptoms may be triggered by allergens, certain drugs, irritants, exercise or emotional stress.  Interactions of cells and mediators may lead to smooth muscle contraction, excessive mucus secretion, mucus plugging of the airways, and may restrict passage of air in airways. Pathogenesis & drug action of Asthma 1. Allergen 2. Triggers IgE 3. Activates mast cells 7. Narrowing of airways by: - bronchospasm - oedema - mucus hypersecretion 6. Secretes mediators which amplify inflammation 4. Mast cells degranulate & release inflammatory mediators 5. Attracts & recruits further inflammatory cells Symptoms of asthma      Breathlessness/ wheezing Cough Occasionally sputum (phlegm) Chest tightness Sleep disturbance Mild asthma symptoms occur no more than twice a week Attacks don’t last long & are alleviated quickly with medication. No symptoms between attacks Moderate asthma Severe asthma symptoms occur almost everyday requires an inhaler almost every time an attack occurs Symptoms are present most of the day, every day Asthma diagnosis Based on: - Medical history - Physical examination - Patient symptoms - Trigger factors Tests of lung function: PEFR - Peak expiratory flow rate FEV1 - Forced expiratory volume during the first second of a forced expiratory vital capacity test As a rule, you are likely to have a disease that causes narrowed airways if: • Your FEV1 is less than 80% of the predicted value for your age, sex and size; or your • FEV1/FVC ratio is less than 0.7. Traditionally, the diagnosis of asthma is based on demonstrating an increase in FEV1 or peak expiratory flow rate (PEFR) of 15% or greater following the inhalation of a bronchodilator. NICE guidelines for the bronchodilator reversibility (BDR) test is as follows: • Offer a BDR test to adults (aged 17 and over) with obstructive spirometry (FEV1/FVC ratio less than 70%). Regard an improvement in FEV1 of 12% or more, together with an increase in volume of 200 ml or more, as a positive test. Consider a BDR test in children and young people (aged 5 to 16) with obstructive • spirometry (FEV1/FVC ratio less than 70%). Regard an improvement in FEV1 of 12% or more as a positive test. COPD  Chronic obstructive pulmonary disease (COPD) is a disease state characterised by airflow limitation that is not fully reversible.  Airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases.  The disease is predominantly caused by smoking and it develops slowly over the years Most common conditions comprising COPD: Chronic bronchitis inflammation in bronchi increases mucus production in the airways, producing phlegm which makes you cough. The presence of cough and sputum production last for at least 3 months in each of 2 consecutive years is a definition of chronic bronchitis. Emphysema characterized by abnormal enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction and collapse of alveoli. This reduces the number of alveoli available for gas exchange. Symptoms: - intermittent airway inflammation leads to frequent, prolonged episodes of productive cough and mucus production - acute episodes of worsening of symptoms including worsening of dyspnoea both on exertion and at rest, wheeze, chronic cough and increase in sputum purulence and volume, commonly called an ‘exacerbation’ - Symptoms will vary in severity from person to person and according to the level of lung function impairment - In most cases, COPD is preventable because the most common cause is cigarette smoking. Diagnosis and assessment Diagnosis should be considered if symptoms of chronic bronchitis are present along with smoking and confirmation of airflow obstruction by spirometry. In patient with FEV1/FVC<0.70: Mild FEV1≥80% predicted Moderate 50%≤ FEV1<80% predicted Severe 30%≤ FEV1<50% predicted Very severe FEV1<30% predicted Management of COPD Most patients with COPD get some symptom relief from bronchodilators and antiinflammatory agents, similar to people with asthma. The goals of effective COPD management are to:  Prevent disease progression  Relieve symptoms  Smoking cessation: cessation counselling and nicotine replacement therapy (NRT),  Reduce mortality  Prevent and treat exacerbations.  Encourage the patients to exercise.  Weight loss is common in patients with advanced COPD - should be educated about nutrition and lifestyle including: o Eating small frequent meals that are dense in nutrient content with sufficient calories. o Fruits and vegetable intake as they contain antioxidants, minerals, vitamins, and fibre. o vitamin supplements:  Vitamin D: The serum levels of vitamin D have been found to be low in patients with COPD, and its deficiency has been related to early progression of COPD.  Vitamin C and E supplementation also plays a promising role in alleviating COPD symptoms. Asthma vs COPD 1. Onset of asthma = childhood, onset of COPD = develops in older smokers 2. Exacerbations of asthma = characterised by recurrent symptoms (wheezing, chest tightness, shortness of breath, cough etc.) Exacerbations of COPD = commonly caused by respiratory tract infections. 3. Treatment for asthma = aims to have near-normal lung function and be symptomfree between exacerbations. COPD patients rarely experience a day without symptoms. Airflow obstruction in COPD sufferers is only partially reversible Maintenance therapy for asthma: inhaled corticosteroid to control inflammation, with the addition of a bronchodilator, when required to control symptoms. Maintenance therapy for COPD: Bronchodilators = first line maintenance treatment for COPD. Treatment with inhaled corticosteroids is reserved only for selected patients whose COPD is not adequately managed with bronchodilators that have severe COPD (FEV1 < 50% predicted) and have frequent exacerbations. History COPD Asthma Smoker/ex-smoker Symptoms under age of 45 Chronic productive cough (typically in the morning) Breathlessness Night wakening with breathlessness/wheeze Nearly all Rare Common Possibly Often Uncommon Persistent & progressive Uncommon Variable Common Infectious lung diseases Pneumonia  Inflammatory condition within the lungs produced as a result of infection that primarily affects the alveoli.  Causes Usually caused by viral or bacterial infections. People are more likely to develop pneumonia while recovering from a cold or flu as the lungs’ ability to fight off infection is compromised. People with asthma, cancer, heart disease or diabetes are more susceptible to pneumonia.  Treatment antibiotics such as amoxicillin, clarithromycin, doxycycline. As pneumonia can be life threatening, people at high risk of pneumonia may be offered a vaccine against the pneumococcal bacteria. Tuberculosis (TB)  Tuberculosis is an infection caused by the Mycobacterium tuberculosis bacteria. This disease is most commonly found in the lungs but it can also affect the other parts of the body because the infection can spread via blood.  It produces symptoms similar to a slowly progressive pneumonia. It breaks down the connections between the air sacs, leading to emphysema.  Treatment usually involves taking antibiotics for several months. The usual treatment is:  two antibiotics (isoniazid and rifampicin) for six months  two additional antibiotics (pyrazinamide and ethambutol) for the first two months of the six-month treatment period OTC medicines Preparation Paracetamol Ibuprofen Oral decongestant Menthol and eucalyptus inhalation Symptoms used to treat/prevent Example of product(s) available OTC Evidence of effectiveness? Headache, sore throat, muscular aches & pains, fever used to reduce inflammation and fever, menstrual cramps provide short-term relief for a blocked or stuffy nose (nasal congestion). ease the symptoms of conditions such as colds and flu, hay fever and other allergic reactions, catarrh and sinusitis. Generic tablets Calpol® liquid Panadol® caps Generic tablets, Nurofen, Ibuprofen gel, oral suspensions Yes – one of the most useful treatments Pseudoephedrine relatively effective for minor congestion For relief of the symptoms of coughs, colds and blocked noses Care Menthol & Eucalyptus Inhalation 100ml lack of evidence to establish its effectiveness. Yes Throat lozenges Antibiotics Echinacea Zinc temporarily suppresses the cough, and lubricates and soothes irritated tissues of the throat. Bacterial infections Soothers, Strepsils, Lockets Lacks evidence In the UK all antibiotics require a prescription. Amoxicillin · Flucloxacillin Prevention and treatment of cold symptoms Treatment and prevention of zinc deficiency, also used for boosting the immune system, treating the common cold and recurrent ear infections, the flu, upper respiratory tract infections, preventing and treating lower respiratory infections Potter's Catarrh & Congestion Relief® Yes, evidence of effectiveness for bacterial infections but not for viral infections. Antibiotic resistance can occur with frequent usage Unsure – evidence conflicting, non-standardised preparations Zinc tablets There is some scientific evidence to support its use for some of these conditions. Inhalation therapy      Most widely used system for drug delivery to the lungs Preferred route for asthma and COPD therapy – rapid onset of action Exert a high local therapeutic effect so smaller doses can be administered 1st pass metabolism in intestines & liver can be avoided Doses required to achieve therapeutic effect are usually 1/10 to 1/5 compared to oral doses, with the remainder deposited in the oropharyngeal and being swallowed.  Lungs may also be used as a route of drug delivery for systemic circulation Nebulisers - Nebulisers convert a solution of drug into an aerosol for inhalation. - Mainly used in hospitals for high doses. - Can deliver high amounts of drugs to patients under normal tidal breathing – useful in children and elderly. - Frequently used for drugs that cannot be formulated into MDI/DPI or if therapeutic dose required is too large for alternative systems. - useful in status asthmaticus & acute hospital treatment of severe asthma. Disadvantages: - Potential for drug delivery in eyes with face mask delivery - Assembly & cleaning required - Contamination is possible - Long inhalation time (10-15 mins) -Residual drug left in chamber is high - requirement for a power supply - Long term use limited by cost, convenience and danger of over-reliance. Dry powder inhalers (DPIs) 3 types: - single unit dose DPI’s (Spiriva) - multiple unit dose DPI’s (Accuhaler, Diskhaler) - multiple dose reservoir device (Turbohaler, Novolizer) These devices use a dry powder consisting of a drug or mixture of drugs and an inert excipient (usually lactose). Upon inhalation, the pressure from inhaling separates the dry powder, and fine particles are carried into airways with inhaled air. Metred dose inhalers (MDIs)      Consists of a canister containing the drugs dissolved or suspended in a propellant (eg- hydrofluoroalkanes, HFA) under pressure. When activated, a valve system releases a metered volume of drug & propellant. Propellant provides force to release and re-aggregate particles. The fast release of the particles causes high oropharyngeal deposition and produces a cooling sensation at the back of the throat, known as cold Freon effect. This may stop some patients inhaling immediately and cause them to deposit a large portion of the dose in the mouth. MDIs require co-ordination between the start of an inhalation and release of the dose from the device – children and elderly may find difficult MDI with spacer is preferred in patients with non-life-threatening acute asthma. Whereas in life-threatening acute asthma, a nebuliser with oxygen is preferred. Spacers and valved holding chambers Add-on devices for MDI’s to improve drug delivery. They reduce oropharyngeal deposition of drug, increase lung deposition & reduce drug loss associated with poor patient coordination. Spacers are particularly effective in children. Disadvantages bulky to carry – could decrease patient compliance. Spacers use a one-way valve and acts as a holding chamber for the drug. This removes the need for patient coordination. Most effective method single-breath technique, but tidal breathing (multiple breath technique) may be used in patients unable to control their breathing - such as elderly, children or when a patient is having an asthma attack. Drug(s ) Seretide Accuhale r 100/50 fluticas one HandihalerRespimatEasyhalerSymbico rt Turbohal er 100/6 tiotropiu m tiotropi um Salmet erol Salbutam ol Budesoni de Beclomet hasone formotero l Used to treat: Asthma Bronchitis Asthma & COPD & COPD emphyse ma, COPD Asthma budes onide formot erol fumara te dihydr ate Combin ation treatme nt for asthma Incruse Ellipta Relvar Ellipta umeclid inium bromid e fluticason e furoate Mainten ance treatme nt for COPD Combina tion treatment for asthma vilanterol trifenatat e Anoro Ellipta vilanterol trifenatat e umeclidini um bromide Maintena nce treatment for COPD Combive nt Salbuta mol Ipatropi um bromid e Combin ation treatme nt for COPD Maintenance and reliever therapy (MART) Combination of regular maintenance (preventer) & treatment (reliever). Combo of a long acting B2 agonist and corticosteroid. For this combo to be effective, it must contain a fast acting long-acting B2 agonist (LABA) such as FORMOTEROL. Benefits steroid dose is increased as patient’s condition worsens - they use more reliever doses. – this prevents exacerbation. As patient’s condition improves, patient can reduce reliever doses and go back to maintenance dose of the steroid. OXYGEN High-flow O2 should be given to all patients in respiratory distress unless they have COPD and a ‘hypoxic drive’. O2 should be given at a lower conc for these. O2 increases alveolar oxygen tension and decreases the work of breathing necessary to maintain arterial oxygen tension. Targets of inhaler therapy and particle size effects The lung deposition of an inhaled drug varies according to inhaler device, inhalation technique and particle size. RESPIRABLE DOSE RANGE 0.5 – 5 μm (particle size that produces therapeutic response) Inhaler devices contain heterodispersed aerosol which is made up of different sized particles. When drug is inhaled, aerosol particles travel to different regions, depending on particle size and can deposit on the respiratory tract at any point from mouth to alveoli. Drug particles less than 2μm tend to be concentrated in the distal airways and alveoli. β2 receptors and airway smooth muscle are present in the small conducting airways. Therefore, the suitable particle size for inhaled β2-agonists = 2–5 µm However, to achieve the broadest and deepest penetration into the lungs, the ideal β2-agonist particle size is approximately 2–3 μm as this range produces greater bronchodilation. Larger aerosol particles (5 - 10 µm) tend to deposit out in the upper airways (nasopharynx and oropharynx) while particles larger than 10µm and 15 µm are generally deposit in the nose and mouth Key factors affecting drug delivery to lungs MDI’s  requires slow and deep inhalation as well as coordination. Slow airflow with less turbulence = more deeply penetrated in lungs  Most important technique = slow and deep inhalation. Failing to do this is the most common mistake made by patients. Fast inhalation rate increases likelihood of oropharyngeal deposition.  For patients who cannot coordinate actuation and breathing, switch to breath-actuated MDI. However, choice of pharmacologic therapy may be limited & unaccustomed delivery may cause a temp cough.  The use of a spacer can reduce oropharyngeal deposition and improve lung deposition. DPI’s  Requires a rapid and forcible inhalation. Patients inhalation required to transform the powder in a DPI to a dose of particles for deposition in the lungs. Turbulent energy is represented by: √∆P= Q × R ∆P pressure drop from turbulent energy inside device after inhaling Q inhalation flow R resistance to airflow For each inhaler there is a minimum energy (inhalation flow) required to provide efficient disaggregation of the formulation. The minimum inhalation flow is important - there is the potential for a patient to receive no dose. Very young (under 5 years), elderly patients and those with severe conditions may not be able to generate the sufficient inhalation flow that produces a dose reaching the lungs from some devices. Failure to use a fast inhalation results in particles that are too big to be deposited in the lungs. This causes the dose to be deposited in the oropharynx and subsequently swallowed. If the inhalation is too fast, the powder may not disaggregate before it leaves the inhaler which will lead to greater deposition in the oropharynx. Optimising inhaler therapy Smoking Nicotine is an alkaloid, which is the principle active agent in tobacco. It acts on the nicotinic receptors – stimulating the release of neurotransmitters – dopamine and mimics action of Acetylcholine. Causes: stimulation and relaxation suppresses the appetite pleasurable effects. Nicotine starts to act on brain within 7 secs after inhalation, giving peak blood concentrations around 30 seconds and has a half-life 2 hours. Smokers self-regulate in order to increase the pleasurable effects and minimise withdrawal symptoms. Nicotine has several cardiovascular effects: • Increases Heart Rate • Raises Blood Pressure • Vasoconstrictor effects • Causes release of Cholesterol into bloodstream Tobacco Smoke contains many dangerous compounds, including: • • • • • • • • • • Carcinogens - tars, Acrolein, Nitrosamines, Radioactive compounds Acetone Ammonia Smoking in pregnancy: Arsenic Benzene  Smoking whilst pregnant can cause Cadmium chemicals from cigarette smoke to enter Carbon Monoxide bloodstream and then into placenta and Cyanide Formaldehyde umbilical cord – into the baby. Shellac (French polish)  This causes baby to struggle for oxygen.  Baby goes through nicotine withdrawal Respiratory effects of smoking include: once born. Causes baby to be stressed and • Lower blood oxygen levels irritable & crying • Paralysis of Cilia  Smoking increases cot death by at least • Tar in lungs 25% • Coughs and Chest Infections • COPD Children exposed to passive smoking are at risk of • Lung Cancer ear infections, bronchitis, pneumonia, asthma attacks and meningitis Smoking cessation Health Benefits of Smoking Cessation: Timescale of health improvements 20 mins pulse rate and BP return to normal 8 hours blood oxygen levels return to normal 48 hours nicotine eliminated from body and your carbon monoxide level drops to zero, sense of taste and smell improve 72 hours breathing is easier, bronchi relax, energy levels increase 2-12 weeks circulation improves, physical activity easier 3-9 months Lung function increased 10%, cilia re-grow, improvement in coughing, wheezing and shortness of breath 1 year Risk of heart disease is halved compared to someone who is still smoking 10 years Halved risk of lung cancer 15 years Risk of having a heart attack or stroke is the same as that of someone who has never smoked Motivators for Smoking Cessation: • Health – long term and short term • Cost • Family, Social, Work pressures • Pregnancy Barriers to Smoking Cessation: • Weight Gain • Social pressures • Not the right time • Withdrawal effects • Can’t break habit, previous failed attempts • Cost of NRT • Enjoy smoking Withdrawal effects: • Irritability • Anxiety • Insomnia • Lack of concentration • Low mood 2 main aspects of smoking addiction – The physical addiction to nicotine, and the “habit” or psychological addiction to smoking and smoking behaviour. The physical addiction lasts for only 2 weeks and can be managed by replacing nicotine and reducing the levels over a period of around 12 weeks. This is called Nicotine Replacement Therapy (NRT). The habit is more difficult to crack, and tends to be the main reason for failure of smoking cessation attempts.