 \200 Diagnosis Renal biopsy usually shows diffuse crescentic glomerulo- nephritis. Linear IgG de position detected by immuno \202 uorescence or immunoperoxidase. Lung biopsy shows active intra-alveolar hemorrhage with collections of haemosiderin laden macrophages. These are not speci \201 c changes, but may also show linear immuno \202 uorescence staining of IgG. D ifferential diagnosis Wegener \200\231s granulomatosis, other pulmonary renal syndromes. Management \200 \200 Involve the renal team and share care of the patient Plasma exchange improves the speed of response to immunosuppres- sion High-dose steroids and cyclophosphamide May need dialysis. Renal function may not improve and renal transplant is only an option later if anti-GBM ant ibody levels become low Recurrence is uncommon once disease is controlled. It usually respo nds to further immunosuppression. Residual defects in PFTs frequent. \200 Prognosis Rapidly progressive pulmonary hemorrhage and renal failure. Usually fatal if not treated. This page intentionally left blank CHAPTER 51 Vasculitis and the lung 660 Churg \200\223Strauss syndrome De \201 nition and epidemiology Asthma, blood eosinophilia, and an eosinophilic granulomatous in \202 ammation of the respiratory tract, with necroti zing vasculitis affecting small and medium sized vessels. \200 Rare, 2.4 per million population, but 64 per million of an asthmatic population (who may ha ve been misdiagnosed with asthma) Middle-aged adults 2 male:1 female Unknown cause. Montelu kast was postulated as a possible cause, but this is now thought unlikely. Development of C hurg \200\223Strauss syndrome in people on montelukast probably related to their decreased steroid dose \200\230unmasking \200\231 Churg \200\223Strauss syndrome, or as part of an i ncreasing treatment regime in those with uncontrolled asthma, later diagnosed as Churg Stra uss syndrome. \200 \200 Clinical features A diagnosis of Churg \200\223Strauss syndrome can be made if 4 of the fol lowing 6 criteria are present: \200 Asthma \200\224may have had for years, often maturity onset, dif \201 cult to control, ass ociated with rhinitis and nasal polyps \200 Blood eosinophilia >10% \200 Vasculitic neu ropathy, such as mononeuritis multiplex (occurs in 75%) \200 Pulmonary in \201 ltrates \200 Sinus disease \200 Extravascular eosinophils on biopsy \201 ndings. (American Col lege of Rheumatology criteria, 1990) \200 Also may have: \200 Myositis and cardiac failure, cardiomyopathy, coronary artery in \202 am- mation, pericard ial effusion Eosinophilic in \201 ltration of mesenteric vessels causing GI disturbance Al veolar hemorrhage Rarely, proteinuria caused by renal disease with focal segmental glo- mer ulonephritis. Renal failure is rare Skin nodules and purpura Myalgia and arthralgia Fever a nd weight loss. \200 \200 \200 \200 Typical pattern of disease has three phases: beginning with asthma, then developing blood a nd tissue eosinophilia, then going on to systemic vascu- litis. The asthma precedes the vas culitis, often by years (mean 8 years). Investigations \200 CXR Fleeting peripheral pulmonary in \201 ltrates and bilateral multifocal consolidation H RCT Ground-glass in \202 ammation, pulmonary nodules, bronchial wall thickening, or alveol ar hemorrhage Bronchoscopy BAL: marked eosinophilia Pathology Extravascular tissue eosinoph ilia, necrotizing angiitis, granulomata Serum markers Peripheral blood eosinophilia. p-ANCA and anti-MPO positive in two-thirds. ANCA levels may not correlate with disease activity, but blood eosinophilia is a good guide. \200 CHURG \200\223STRAUSS SYNDROME 661 Diagnosis Predominantly a clinical diagnosis. Pathological con \201 rmation of eosinophili c tissue in \201 ltration or vasculitis desirable. Biopsy easiest site affected, such as s kin, kidney, or open or thoracoscopic lung biopsy. Differential diagnosis Allergic bronchop ulmonary aspergillosis, sar- coidosis, drug and parasitic causes of eosinophilic pneumonias , hypersensi- tivity pneumonitis, hypereosinophilic syndrome. Management Depends on severit y of disease at presentation. \200 If isolated pulmonary disease, oral prednisolone 1 mg/kg (max 60 mg/ day) for 1 month or un til no evidence of disease, then slowly decrease over 1 year, with increases if symptoms re cur If unwell, or with alveolar hemorrhage, pulsed methylprednisolone IV for 3 days, follow ed by high-dose oral steroids, with or without cyclo- phosphamide (see p 678 and 680) In ca rdiac or GI disease, relapse, or life-threatening situations, such as requiring organ suppo rt, cyclophosphamide should be added (see p 680) Plasma exchange is of no bene \201 t Trea tment is aimed at reversing organ damage and reducing relapse rate To maintain remission, p rednisolone and one other immunosuppres- sant drug are usually required. Cyclophosphamide i s often changed to azathioprine after 4 \200\2236 months Prophylactic co-trimoxazole should be given (960 mg 3 \227/week) and consider bone protection for steroids Follow-up: regular ly, with checks on FBC and eosinophil count, CXR. Prognosis Good prognosis if isolated pulm onary disease. Good response to steroids. May continue to have asthma despite control of va sculitis, which can be severe and dif \201 cult to control. Poor prognosis associated with cardiac disease and severe gastrointestinal disease, causing bleeding, perforation, or nec rosis. Untreated, 5-year survival rate is 25%. Also associated with worse prognosis: protei nuria >1 g/24 h, renal insuf \201 ciency, CNS involvement. Cardiac disease is the main cau se of death. \200 Further information Noth I et al. Churg \200\223Strauss syndrome. Lancet 2003; 361: 587 \200\22394 www.vasculitis.org 662 CHAPTER 51 Vasculitis and the lung Rare pulmonary vasculitides Polyarteritis nodosa \200 \200 \200 \200 Similar to microscopic polyangiitis, but affects medium-sized vessels May exist as an \200 \230overlap \200\231 disorder with Wegener \200\231s or Churg \200\223Strauss Lung involvem ent is rare Sometimes associated with previous hepatitis B or rarely hepatitis C infection. Takayasu \200\231s arteritis \200 \200 Predominantly young women, often Asian Vasculitis affecting the aorta and its major branche s. Large and medium-sized pulmonary vessels affected, but involvement is usually silent. Pu lmonary artery stenosis and occlusion common, occasionally with mild pulmonary hypertension Presents with fevers and weight loss. Absent or weak upper limb peripheral pulses, particu larly on left (as left axillary artery comes off aortic arch) and arterial bruits Diagnosis made by angiography Treatment Steroids may reduce symptoms, but do not affect mortality. A ngioplasty and surgical procedures may reduce the complications. Spontaneous remissions may occur. \200 Giant cell arteritis \200 Commonest form of systemic vasculitis affecting large- and medium- sized vessels 24 cases p er 100 000. Predominantly elderly females Presents with non-speci \201 c symptoms of fever and weight loss, also headache, scalp tenderness, and jaw pain. Amaurosis fugax and visual loss due to optic neuritis Pulmonary complications occur in 9 \200\22325% of cases. They a re relatively minor, with cough, sore throat, and hoarseness. Pulmonary function tests and CXR normal Diagnosis High ESR, temporal artery biopsy showing pan-arteritis and giant cell formation Treatment Good response to oral steroids. Continue for 1 \200\2232 years. \200 Part 00 Part 3 Supportive care 52 Ethical issues 53 Financial entitlements 54 Immunosuppressive drugs 55 Inhalers and nebu lizers 56 Intensive therapy unit (ITU): when to involve 57 Non-invasive ventilation 58 Oxyg en therapy 59 Palliative care 60 Pulmonary rehabilitation 61 Smoking cessation 62 Tracheost omy 665 671 675 683 689 693 703 713 723 729 735 This page intentionally left blank 665 Chapter 52 Ethical issues Background 666 COPD 668 Lung cancer and neurological disease 670 CHAPTER 52 Ethical issues 666 Background Most ethical issues faced by doctors arise at the end of a patient \200\231s lif e. This particularly applies to respiratory physicians, where dif \201 cult decisions abou t the appropriateness of treatment and the prolongation of life in patients with chronic un derlying lung disease may need to be made. In some situations arti \201 cial ventilation m ay prolong the dying process; life has a natural end and the potential to prolong life in t he intensive care unit can sometimes cause dilemmas. The General Medical Council (GMC) states that doctors have an obli- gation to respect human life, protect the health of their patients, and put their patients \200\231 best interests \201 rst. This means offering treatments where the bene \201 ts outweigh any risks, and avoiding treatments that carry no net gain to the patient. If a patient wishes to have a t reatment that in the doc- tor \200\231s considered view is not indicated, the doctor and me dical team are under no ethical or legal obligation to provide it, but the patient \200\231 s right to a second opinion must be respected. The discussion about resuscitation and formal ventilation is never an easy one, but should ideally be taken with nursing staff, the patient, and their next of kin, in advance of an e mergency situation. In practical terms, clearly this is not always possible. Ideally all de cisions regarding resusci- tation and the ceiling of treatment (particularly relating to ve ntilation) should be documented in advance, and handed over to the on-call team. Most possi ble outcomes can be anticipated. Where it has been decided that a treatment is not in the best interests of the patient, the re is no ethical distinction between stopping the treat- ment, or not starting it in the \201 rst place (though the former may be more dif \201 cult to do), and this should not be used as an argument for failing to initiate the treatment in the \201 rst place. Some clinical scenarios are more commonly encountered by the respi- ratory physician. These are discussed on the next pages. This page intentionally left blank CHAPTER 52 Ethical issues 668 COPD COPD is the 4th commonest cause of death in America, and most patients die of respirat ory failure during an exacerbation. A commonly encoun- tered clinical situation is where a patient with COPD is admitted with an exacerbation, and is in type II respiratory failure. Standard treatment does not improve the respiratory acidosis, so non-invasive ventilation i s com- menced. Before starting NIV, a decision must be clearly documented as to whether or not NIV is the ceiling of treatment. It may be, especially if the patient has severe or end -stage COPD. Formal ventilation in the intensive care unit may be appropriate in certain speci \201 c situations; for example: \200 \200 In a relatively young patient (i.e. <65 years) A patient with a relatively new diagnosis of COPD, in whom the episode is the \201 rst or second admission In the patient in whom the re is a very obviously potentially reversible cause for the exacerbation, e.g. pneumonia Sometimes in this situation, a de \201 ned time period for intensive care input may be dec ided, e.g. ventilation for 48 h (to allow treatments to work and to allow time to assess fo r any improvement), with extubation after that time period if no improvement has been made. Decisions about formal ventilation and intensive care admission can only be made with knowl edge of the patient \200\231s usual level of functioning and previous quality of life. The dif \201 culty in this situation is that quality of life is a very subjective measure. Obj ective measures of usual functioning, such as measures of daily activity, usual exercise to lerance, and whether home care or assistance with activities of daily living is required ar e more useful in guiding the appropriateness of escalating therapy. With particular referen ce to the patient with COPD, the number of hospital admissions and exacerbations, and the n eed for home oxygen or nebulizers will also be useful. Helpful information may be obtained from the GP, especially if the previous hospital notes are unavailable. Neither the next of kin nor those with Enduring Power of Attorney (EPA) have the legal righ t to determine any treatment; the responsibility remains with the doctor and multidisciplin ary team, occasionally involving the courts of law. Lasting Power of Attorney (LPA) replace d EPA from October 07. This allows an appointed attorney to make decisions about personal w elfare, including giving or refusing consent to treatment, if the patient loses their capac ity. Where limited information is available about the patient and therefore uncertainty exists a bout the appropriateness of ventilation, it should be started until a clearer assessment ca n be made. This may be relevant for a patient attending the accident and emergency departme nt, in whom little information is available. The above point concerning the withdrawal of t herapy, should it subsequently be found to be inappropriate, also holds. COPD 669 There are downsides to invasive ventilation: the risk of pneumothorax is increased in those with end-stage emphysema, and the risk of ventilator- acquired pneumonia increases with ti me ventilated. Knowledge of the risk of these adverse events helps the medical team to bala nce the argument and make a decision about whether the risks of ventilation are likely to o utweigh its bene \201 ts. The issue of limited resources should not in \202 uence a decis ion about formal ventilation or ITU admission. The average length of intubation of patients with COPD admitted to ITU is 3.2 days. These p atients have a 20 \200\22325% in-hospital mortality, with 50% of patients surviving 1 year post-ITU discharge. About 50% will be living independently 1 year post-hospital discharge. Clearly, only a very selected subgroup of patients are admitted to ITU, but concerns about prolonged periods of ventilation in this group of patients seem to be unfounded. Patients i n whom a clear cause for the exacerbation can be identi \201 ed (e.g. pneumonia) tend to d o better, as there is a treatable cause for the exacerbation and not just progression of th e underlying disease. CHAPTER 52 Ethical issues 670 Lung cancer and neurological disease Lung cancer The use of antibiotic treatment for pneumo nia in a patient with advanced lung malignancy may be inappropriate in some circum- stances . The stage and extent of disease, response to other treatments (e.g. chemotherapy), and th e patient \200\231s wishes and quality of life are all para- mount. This is another situati on in which it might be appropriate to de \201 ne at the outset the treatments that are ap propriate, e.g. 10 days total of intravenous and oral antibiotics. Note that treatments suc h as antibiotics can lead to improvement in symptoms (e.g. by reducing fever), without nece ssarily prolonging life, and it may be kinder to continue antibiotics in this situation. Pr ogressive neurological disease The decision about non-invasive ventilation in a patient wit h a progressive neuromuscular disease can be dif- \201 cult. In this setting the clinical deterioration can usually be anticipated, and in most situations, discussion should have t aken place early on (unless the patient presents in respiratory failure, for example, due t o pneumonia, and subsequent ventilator weaning is dif \201 cult). Different centers, patie nts, and their relatives will have differing views as to whether life-prolonging non- invas ive ventilation in the face of progressive neuromuscular disability is warranted. Some cent ers take the view that if the quality of life and higher mental functioning are good, and t he respiratory muscles are affected early on (and other functions and mobility remain good) , then NIV is war- ranted. Further decisions about withdrawal of treatment with progression of the underlying neurological disease of course will still be needed. In, for example, mo tor neuron disease with bulbar palsy, aspiration is a rela- tive contraindication to non-in vasive/mask ventilation. Aspiration in these patients is a poor prognostic sign, and often a sign of imminent death. Advance directive documents the patient \200\231s wishes in the e vent of serious illness. It will usually include a decision about resuscitation and other p otential life-prolonging treatments. The patient must understand the implications of his/he r decision. Further information Withholding and withdrawing life-prolonging treatments: good practice i n decision-making. General Medical Council 2002 671 Chapter 53 Financial entitlements Patient \201 nancial entitlements 672 CHAPTER 53 Financial entitlements 672 Patient \201 nancial entitlements Patients with chronic lung disease and their carers may be eligible for \201 nancial support. There are a large number of potential bene \201 t s that can be claimed, and the process is often time-consuming and complicated. The best so urces of information are: \200 \200 \200 \200 Bene \201 ts Enquiry Line 0800 882200 (0800 220674 in Northern Ireland) Website www.dwp.go v.uk. Forms can be completed on-line The Citizens Advice Bureau www.nacab.org.uk The ward s ocial worker is usually a good source of information Patients who are unable to work may be eligible for: Statutory sick pay (SSP) A doctor \200 \231s certi \201 cate is usually required for more than 1 week \200\231s sick pay. New rul es now make the doctor \200\231s certi \201 cate the responsibility of the hospital consul tant under whom the patient was admitted, and it should be completed on discharge, to cover the advised period off work. This also applies to patients needing time off work, but not admitted to hospital. Nursing staff usually complete the forms for the period during which the patient was in hospital. Incapacity bene \201 t is more complicated and is paid to peo ple not eligible for SSP. It runs for up to a year. After 196 days (the \201 rst period i s usually covered by a medical certi \201 cate) the patient may have to pass a personal ca pability assessment to show they are incapable of work. Severe disablement allowance Income-related bene \201 t Bene \201 t for the extra cost of disability Disabled persons tax credit (DPTC) This is not a bene \201 t as such, but a ta x credit from the Inland Revenue (paid in addition to bene \201 ts). Severe disablement al lowance if a test of 80% disablement is passed. Disability living allowance or attendance a llowance are bene \201 ts for the extra costs of disability and depend on age (>or <65 yea rs) Costs for care needs and mobility needs Industrial diseases disablement bene \201 t. See p neumoconiosis p 363 and asbestosis p 118. PATIENT FINANCIAL ENTITLEMENTS 673 Reduced earning allowance Form DS1500, the \200\230special rules form \200\231, is for mor e urgent bene \201 ts for patients with terminal disease, in whom life expectancy is not l ikely to exceed 6 months. Patients with a terminal illness can also usually claim attendanc e allowance, incapacity bene \201 t, and disabled living allowance under \200\230special rules \200\231. This means that the claim is processed as a priority, with no qualifying pe riod, allowing higher rates of payment, and without the individual having to prove how much care is needed. The application can be made on behalf of the patient, who does not have to sign the form. This may be appropriate if the patient has not been told the exact details of their life expectancy. Further information There are a number of charities who give grants/aid towards the cost of buying equipment. www.charitiesdirect.com www.charity-commission.gov.uk This page intentionally left blank 675 Chapter 54 Immunosuppressive drugs Patient advice and monitoring 676 Corticosteroids and azathioprine 678 Methotrexate and cyc lophosphamide 680 CHAPTER 54 Immunosuppressive drugs 676 Patient advice and monitoring Immunosuppressive drugs are used mainly in the management of pulmo- nary vasculitis, but also in asthma, sarcoidosis, and interstitial lung diseases. Ce nters differ in their use of these drugs and local guidelines are often available. General advice for patients on immunosuppressive drugs \200 Increased risk of infections and increased likelihood of severe infec- tions. Check FBC if develop febrile illness May have atypical presentation of infections Avoid live vaccines, s uch as measles, mumps, rubella, BCG, yellow fever, oral typhoid, oral polio If never had va ricella zoster: \200 \200 \200 \200 Avoid measles exposure. Prophylaxis with immuno globulins if exposed. \200 Avoid contacts with chickenpox or shingles Consider passive immunization Immunoglobulin the rapy if exposed Hospital treatment with close monitoring if develop chickenpox Table 54.1 Summary of tests to perform before and during immuno- suppressive drug treatment Drug Check before starting Follow-up Corticosteroids BP, glucose. Consider bones/osteoporosis BP, glucose if symptoms of diabetes Azathioprine FBC, LFT, TMPT test (see text) FBC every 2 weeks for 3 months, then monthly LFT monthly Methotrexate FBC, U&E, LFT CXR Folic acid Bloods every 2 weeks for 3 months, then monthly Cyclophosphamide FBC, U&E, LFT Urine dip Semen store Check all every week for 1 month, then every 2 months This page intentionally left blank CHAPTER 54 Immunosuppressive drugs 678 Corticosteroids and azathioprine Corticosteroids \200 First-line treatment for suppressing in \202 ammation. At high doses, also cause immunosup pression. Ineffective as sole therapy for induction of remission in systemic vasculitis IV methylprednisolone (500 \200\2231000 mg/day) for 3 \200\2235 days can be used for aggressiv e induction of remission, e.g. Wegener \200\231s granulomatosis, fol- lowed by maintenance oral steroids (prednisolone 30 \200\22340 mg/day) Usually taken in the morning as they may disturb sleep Dose should be slowly reduced when control of the disease is achieved. Gastri c and bone protection may be necessary as the patient will be on high doses for some months . Also ensure BP and glucose are controlled Ensure patients have steroid treatment card. \200 Side-effects include skin and hair thinning, obesity, cataracts, diabetes, and aseptic bone necrosis. Inform patient of these and document. PCP infection can occur secondary to stero id treatment, particularly with high doses for prolonged periods. Some centers use PCP prop hylaxis. Steroids and osteoporosis Current guidelines suggest patients being started on long-term st eroids, with one other osteoporosis risk factor (such as being over 65 or having had a prev ious osteoporotic fracture), should also start on a bisphos- phonate. In other patients who will be on 7.5mg/day or more for more than 3 months, consider checkin g bone mineral density via DEXA scan of hip and spine, and offer lifestyle advice and bisph osphonates if this is reduced (T score \200\2231.5 or lower). (see Royal College of Physic ians guidelines, www.rcplondon.ac.uk and National Osteoporosis Society, www.nos.org.uk) Azathioprine \200 Mainly used as a steroid-sparing agent, or when vasculitis is under control to enable cyclo phosphamide to be stopped. Takes approx. 4 weeks to work Cytotoxic drug, less effective tha n cyclophosphamide. May be reason- able alternative if side-effects of cyclophosphamide are unacceptable Maximal effect on disease may not be evident for 6 \200\2239 months, but can be used long term TPMT (thiopurine methyltransferase) testing should be performed prior to commencement. TPMT breaks down azathioprine to an inac- tive product. 90% of the population have normal TPMT levels, 10% have intermediate activity, so azathioprine should be given w ith caution; 0.3% have no TPMT activity and azathioprine should be avoided CORTICOSTEROIDS AND AZATHIOPRINE 679 For vasculitis, start with 2 mg per kg/day after cyclophosphamide. Maximum dose usually aro und 150 \200\223200 mg/day As steroid sparing regime: could start 50 mg od for 2 weeks, inc reasing to 100 mg od for 2 weeks, if FBC satisfactory and increasing to 150mg od (or 75mg b d) after further 2 weeks FBC satisfactory. Reduce pred- nisolone by 5 mg every 4 weeks Chec k FBC every 2 weeks for 6 weeks, then at 2 and 4 weeks after each dose increase and thereaf ter monthly. Check LFTs monthly. Stop treatment if WCC <3, platelets <100, or ALP and trans aminases 3 \227 normal. Restart when they recover. Side-effects include sore mouth, ulcers, nausea and vomiting, diarrhea, skin rash, alopecia (rare). Most respond to stopping the drug and restarting at a lower dose. Interacts with a llopurinol and leads to increased toxicity. CHAPTER 54 Immunosuppressive drugs 680 Methotrexate and cyclophosphamide Methotrexate \200 \200 Can be used as a second-line treatment Dose: 7.5 \200\22325 mg once/week. Usual starting do se is 10 mg. Can increase after 6 weeks to 15 mg, in increments of 2.5 mg weekly Baseline C XR. Monitor FBC, U&E, and LFTs every 2 weeks for 3 months then monthly. Give folic acid 5 m g 3 \200\2234 days after dose, to reduce toxicity. Side-effects include mouth ulcers, skin rashes, nausea, macrocytosis, mye- losuppression, p neumonitis (dyspnoea and dry cough). Avoid if signi \201 cant renal or hepatic impairment, or if pleural effusions or ascites, as it can accumulate in these \202 uids. Stop if WCC <3, platelets <100, transaminases 3 \227 normal, pneumonitis. Cyclophosphamide \200 \200 \200 The primary cytotoxic drug used for treating systemic vasculitis Causes immunosuppression w ithout anti-in \202 ammatory effects Used particularly if there are life- or organ-threate ning features, e.g. ventilation for lung vasculitis, systemic features, renal involvement T akes 12 \200\22314 days to work; hence is combined with high-dose steroids at the beginning of treatment. When combined with steroids, it induces remission of vasculitis in 90% of pa tients Perform a baseline urine dip for blood prior to treatment (although note microscopic haematuria is common with active vasculitis). Check routinely for macroscopic haematuria i n patients receiving IV cyclo- phosphamide and, if it is present, stop drug and arrange cys toscopy (rare if mesna is used, and rare with oral cyclophosphamide regimes) PCP prophylaxi s with co-trimoxazole is recommended (960 mg 3 \227/week) in patients receiving cyclophosph amide and prednisolone Semen storage for men prior to starting treatment. Usual treatment duration of cyclophosphamide is 3 \200\2236 months. Courses longer than 6 m onths should generally be avoided; they are no more effec- tive and carry the risk of side- effects from the cumulative dose. Induce remission with cyclophosphamide and prednisolone a nd maintain remis- sion with prednisolone and another immunosuppressant (azathioprine, or m ethotrexate) for at least 2 years. Side-effects Haemorrhagic cystitis is a potentially seri ous side-effect of cyclophosphamide therapy. Risk of bladder cancer is increased (and is gr eater with increasing cumulative dose), and inde \201 nite monitoring of urinalysis 3 \200 \2236-monthly after treatment with cyclophosphamide is recom- mended. Other side-effects in clude nausea, vomiting, infection (including PCP), hair thinning or alopecia, bone marrow s uppression (2%), leucopenia, infertility, lymphoma (0.7%) and leukemia, pulmonary and bladd er \201 brosis. Risk of cervical cancer may be higher \200\224recommend annual cervical s mear for 3 years, and thereafter as per population screening program. METHOTREXATE AND CYCLOPHOSPHAMIDE 681 Cyclophosphamide regimes Oral cyclophosphamide is used if possible in active vasculitis, at a dose of 2 mg/kg (up to 200 mg/day). Reduce dose in elderly (by 25% if >60 years, and by 50% if over 75 years) and in setting of renal impairment Monitoring Check FBC and renal fun ction weekly for the \201 rst month, 2-weekly for the 2nd and 3rd month, and monthly ther eafter. \200 If WCC <4 \227 109/L, neutrophils <2 \227 109/L, stop oral cyclophospha- mide and restart with dose reduced by at least 25 mg when WCC recovered, and then monitor weekly for 4 week s If prolonged (WCC <4 \227 109/L, neutrophils <2 \227 109/L for >2 weeks) or severe (WCC <1 \227 109/L, neutrophils <0.5 \227 109/L) leucopenia/ neutropenia, stop cyclophosphami de and restart at 50 mg daily when WCC recovered; then increase to target dose weekly, WCC permitting If WCC is falling (<6 \227 109/L and fall of >2 \227 109/L since previous coun t), reduce dose by 25%. Pulsed intravenous cyclophosphamide is given if patients cannot take oral preparations, usi ng doses of 15 mg/kg (reduced for age and renal function, maximum dose 1500 mg) every 2 wee ks for the \201 rst 3 pulses and then at 3-weekly intervals. The lowest white cell count occurs 10 days after a pulse. A randomized study has shown that pulsed doses give a lower c umulative dose than oral regimes, but there is no difference in remission rates between the two. The infection rate is higher with oral regimes (European Vasculitis Study Group). If giving IV cyclophosphamide, patients should be well hydrated before (1 L normal saline) and after (3 L/day oral \202 uids for 3 days), and given mesna, which chelates with the u rotoxic cyclophosphamide metabolite, acrolein. Dose varies according to the cyclophosphamid e dose and is available on product literature. Give during cyclophosphamide infusion, and a lso 4 and 8 h after. Prescribe anti-emetics. Monitoring Check FBC and renal function on day of pulse or previous day. \200 If WCC <4 \227 109/L, neutrophils <2 \227 109/L, postpone pulse until WCC >4 \227 109/L, neutrophils >2 \227 109/L, whilst checking FBC weekly, and reduce dose by 25% After \201 rst pulse, check FBC between days 10 and day of next pulse: reduce dose of next pulse by 40% of previous dose if WCC nadir 1 \200\2232 \227 109/L or neutrophil nadir 0.5 \200 \2231.0 \227 109/L Reduce dose of next pulse by 20% of previous dose if WCC nadir 2 \200 \2233 \227 109/L or neutrophil nadir 1 \200\2231.5 \227 109/L Thereafter check FBC on day of pulse or previous day, unless dose adjustment when checked additionally at day 10. Further information Lapraik C et al. British Society of Rheumatology and British Heath Prof essionals in Rheumatology guidelines for the management of adults with ANCA associated vasc ulitis. Rheumatology 2007; 46: 1615 \200\22316 This page intentionally left blank 683 Chapter 55 Inhalers and nebulizers Background 684 Different inhaler types and instructions for their use 686 CHAPTER 55 Inhalers and nebulizers 684 Background Inhalers \200 There are many different inhaler devices that deliver drugs directly to the airways Ideally patients should try a range of devices to choose the most appropriate for them Patients sh ould receive advice on techniques for inhaler use. Technique should be checked regularly, a nd if patients cannot manage a particular device, they should be switched to another The pe rcentage of a drug delivered to the airway varies for each device (from 15% to 60% accordin g to the manufacturers) and depends on good technique Spacer devices improve this delivery and are particularly useful for the elderly, children, and those who \201 nd it dif \201 cult to coordinate inhaler administration with breathing Try to use the same inhaler devic e for all the drug classes used by a patient Advise the patient how to recognize when a dev ice is empty: some have dose counters; others are shaken to hear if they still have content s Titrate inhaler doses with clinical response. Nebulizers are used by patients who gain greater relief from nebulized therapy than from in haled therapy. This may be during acute respiratory illnesses, because of disease severity, or because they are unable to use inhalers. Patients who are being considered for nebulize r therapy should be referred to a respiratory physician. If antibiotics are being nebulized , a more powerful nebulizer is required. How to use Open the ampoule containing the drug so lution and squirt the solution into the nebulizer chamber. Salbutamol and ipratropium bromi de can be taken together, but nebulized budesonide or antibiotics should be used separately . If ipratropium bromide only is being used, this should be delivered via a mouthpiece, as it can lead to glaucoma if used via a mask. Reattach the chamber to the nebulizer mask or m outhpiece. Put the mask over nose and mouth, or position mouthpiece between the lips in the mouth. Switch the nebulizer machine on. Breathe slowly in and out. Continue until all the solution is gone. Switch off the machine. Rinse the nebulizer chamber with hot soapy water after each use. If nebulization takes more than 10 min, change the neb-set (mask, chamber, tubing \200\224lasts 1 \200\2233 months). If no improvement, consider servicing the machine . If the patient is using oxygen, this can still be used during nebulization, either via na sal prongs under the nebulizer mask or by using oxygen tubing attached directly to the nebu lizer chamber to drive the nebulization; at home most cylinders do not provide suf \201 ci ent \202 ow rates to allow this. Nebulizer machines should be serviced annually. This page intentionally left blank CHAPTER 55 Inhalers and nebulizers 686 Different inhaler types and instructions for their use Table 55.1 Different inhaler types Generic name of drug (with product names) Mechanism of action Short-acting 2 agonist Duration 3 \200\2235 h Inhaler color Salbutamol (Ventolin , Asmasal , Pulvinal , Salbutamol, Salamol , Salbutamol Cyclocaps , Airomir , Asmasal Clickhaler , Salamol Easi-Breathe ) Terbutaline (Bricanyl ) Salmet erol (Serevent ) Formoterol (Foradil , Oxis , Atimos Modulite ) Ipratropium bromide (At rovent ) Ipratropium and salbutamol (Combivent ) Tiotropium (Spiriva ) Blue Long-acting 2 agonist Duration 12 h Green Green/turquoise Short-acting anticholinergic White/gray Gray Handihaler , Respimat Long-acting anticholinergic Beclometasone dipropionate (Becotide , Becloforte , Pulvinal , Beclometasone, Beclometha sone Cyclocaps , AeroBec , AerobecForte , Asmabec Clickhaler , Beclazone Easi-Breathe , Qvar ) Budesonide (Pulmicort , Budesonide Cyclocaps , Novolizer ) Fluticasone propion ate (Flixotide ) Mometasone furoate (Asmanex ) Ciclesonide (Alvesco ) Corticosteroid Brown Brown Red Red Red Salmeterol and \202 uticasone (Seretide ) Eformoterol and budesonide (Symbicort ) Sodiu m cromoglicate (Intal , Cromogen Easi-Breathe ) Neocromil sodium (Tilade ) Combination steroid and bronchodilator Purple Red and white Unknown, stabilize Yellow and white mast cells DIFFERENT INHALER TYPES AND INSTRUCTIONS FOR THEIR USE 687 Table 55.2 Instructions for use of different inhaler types Type of device Instructions for use Pressurized aerosol Remove the mouthpiece and shake the inhaler well. Hold the inhaler upri ght with the thumb on the base below the metered dose mouthpiece and the \201 rst \201 nger on the metal canister. inhaler (MDI) Aerosol Evohaler Breathe out as far as is comfo rtable then place the mouth piece between the teeth and close lips around it. Do not bite i t. As you start to breathe in through the mouth, press on the top of the inhaler to release the medication whilst still breathing in steadily and deeply. Hold your breath, take the i nhaler from your mouth, and continue holding your breath for up to 10 s if possible. Wait 3 0 s prior to taking second puff. Use with spacer device to improve drug delivery. CFC-free inhalers need washing every 2 \200\2233 weeks, as they can block. Spacer Nebuhaler Nebuchamber Volumatic Aero Chamber Able Spacer PARI Vortex Space r , Pocket Chamber OptiChamber OptiHaler Ensure spacer is compatible with patient \200\231s inhaler. Remove cap of inhaler and shake it. Insert it into end of spacer device. Place the other end of the spacer in the mouth. P ress the inhaler canister once to release one dose of the drug. Take one deep breath in and hold, or take 3 \200\2234 steady breaths in and out. Repeat as indicated. Valve should rat tle. Clean the spacer once a month with mild detergent, rinse, and air-dry. Replace after 6 \200\22312 months. Breath-actuated devices Autohaler Easi-breathe If an autohaler, remove the cap and lift the red lever. Insert device into mouth. Inhale sl owly and deeply. Continue inhaling when the device \200\230clicks \200\231. Hold breath fo r up to 10 s if possible. Slowly breathe out. To take a second inhaled dose, lower the red lever and lift again. If an Easi-breathe, open the hinged cap. Insert device into mouth. In hale slowly and deeply. Continue inhaling when the device \200\230clicks \200\231. Hold br eath for up to 10 s if possible. Slowly breathe out. Close the cap and reopen for further d oses. If Easi-breathe spacer used, it will need to be removed between each inhalation so th at cap can be opened and closed. Dry powder devices Prime the device. Turbohaler: hold upright, remove the Accuhaler cap, twist the base as far as possible until the click is Turbohaler heard and then twist back again. Clickhaler: shake the Clickhaler device, remove the cap, click the top down and r elease. Twisthaler: remove the cap by twisting and the dose is Twisthaler Easyhaler then ready. Accuhaler: Open inhaler cover, mouthpiece Cyclohaler facing you and push lever dow n to pierce the blister Aerocaps Spincaps containing dose. Diskhaler: insert disc into device by Novolizer opening and pulling out mouthpiece section. To prepare dose, lift up back of lid to 90 un til the blister is pierced, then lower the lid. To use all the devices, hold them level, ex hale fully, place the mouthpiece into mouth between teeth, and inhale steadily. Hold your b reath and remove the inhaler. For a second dose, repeat the above actions. 688 CHAPTER 55 Inhalers and nebulizers Table 55.2 Instructions for use of different inhaler types \200\224(contd.) Type of device Instructions for use Handihaler Flip lid and white mouthpiece open and insert capsule. Close the mouthpiece back down until it clicks. Pierce the capsule by pressing the green button at the side. Exhale as far as i s comfortable. Place mouthpiece into mouth and breathe in slowly and deeply. Remove inhaler from your mouth and hold your breath for 10 s if possible. Slowly breathe out. Repeat if n ecessary to ensure all the powder from capsule is gone. Respimat Hold inhaler upright with cap closed. Turn the transparent base until it clicks. Open the c ap. Breathe out slowly and insert the mouthpiece and seal with lips. Point towards the back of the throat. While taking a deep breath, press the button and continue to breathe. Hold your breath for 10 s if possible and breathe out slowly. 689 Chapter 56 Intensive therapy unit (ITU): when to involve PAR (patient at risk) scoring system 691 CHAPTER 56 Intensive therapy unit (ITU) 690 Ideally communicate with ITU early, as it is much better that they know about a potentially sick patient who may need ITU input, than to \201 nd your patient (and you!) in dif \201 culty later on, with no ITU bed.