 \200 Examination may be normal. Clubbing, basal crepitations, and cor pul- monale are all recogn ized, depending on the severity of the resulting lung disease. IDIOPATHIC PULMONARY HAEMOSIDEROSIS 621 Investigations The diagnosis is one of exclusion, with no evidence of other organ involveme nt. The main differential diagnosis is Goodpasture \200\231s syndrome, Wegener \200\231s gr anulomatosis, SLE, and microscopic polyarteritis. \200 Blood tests Microcytic, hypochromi c anemia, with low iron levels. ANCA, dsDNA, and anti-GBM antibodies should be negative CXR May show transient patchy in \201 ltrates, which worsen during an acute bleed. The apices are usually spared. Progressive disease leads to the development of reticulonodular in \201 ltrates, and a ground-glass appearance that is typically perihilar or in the lower zon es. Hilar lymph- adenopathy may be seen PFTs kCO is transiently elevated during bleeding ep isodes ( \211 130% is abnormal), but this is only useful acutely. A restrictive defect with reduced kCO may develop with chronic disease CT chest The changes seen are fairly non-spec i \201 c, showing a diffuse bilateral in \201 ltrate, with patchy ground-glass change BAL (if done) contain haemosiderin-laden macrophages. Management There is no speci \201 c treatment. \200 Steroids and immunosuppressive drugs may be of bene \201 t during acute bleeding episodes, but do not appear to affect the long-term outcome. There are no published data to guide th e optimal timing of treatment during the course of disease The iron de \201 ciency anemia responds to replacement therapy, and blood transfusion may be needed in severe bleeds. At routine clinic appointments \200 \200 \200 Check spirometry Measure hemoglobin and serum iron levels Ask about increases in SOB or hae moptysis. Prognosis The prognosis is very variable, with some patients showing spontaneous remission. The duration of disease in the literature ranges from death within days following an acute severe illness, to survival with cor pulmonale associated with chronic disease after 20 ye ars. 622 CHAPTER 49 Unusual conditions (BOLD) Langerhans \200\231 cell histiocytosis De \201 nition Pulmonary Langerhans \200\231 cell h istiocytosis (LCH; previously termed pulmonary histiocytosis X or pulmonary eosinophilic gr anuloma) is a rare condition characterized by in \201 ltration of the lung with histiocyte s (Langerhans \200\231 cells). Pulmonary LCH overlaps with a number of other con- ditions w ith similar pathological \201 ndings but diverse clinical features. These range from loca lized in \201 ltration of a single organ (e.g. eosinophilic granu- loma of bone) to system ic diseases affecting multiple organs (Letterer \200\223 Siwe disease, a multi-organ diseas e affecting infants and elderly, associated with poor prognosis; also Hand \200\223Schuelle r \200\223Christian syndrome). Although the isolated pulmonary form most commonly presents to chest physicians, pulmonary manifestations also commonly occur in the systemic forms of the disease. Epidemiology Rare, it tends to affect young adults aged 20 \200\22340 years. T he vast majority of cases occur in current smokers, usually heavy smokers. May be more comm on in men, who tend to present at a younger age than women. Pathogenesis Langerhans \200 \231 cells are involved in antigen presentation, and are characterized by the presence of w ell-demarcated cytoplasmic organelles called Birbeck granules on electron microscopy. The L angerhans \200\231 cells seen in LCH appear to be monoclonal, although it is unclear if thi s represents a true neoplastic process. The antigen stimulus for activating Langerhans \200 \231 cells in the lung is unknown, although cigarette smoke is a possible candidate. Langer hans \200\231 cells are typically organized into granulo- mata that are located in bronchio lar walls, and subsequently enlarge and invade adjacent structures. This results in the rad iological appearance of nodules that at \201 rst cavitate and then become cystic. Clinica l features Typically exertional breathlessness and cough, some- times with systemic symptom s (e.g. fever, weight loss). Pneumothorax occurs in at least 10% of patients and may be the presenting feature. Rib lesions may also give rise to chest pain. Around 25% of patients a re asymp- tomatic. Examination is usually normal. Investigations \200 CXR Typically diffuse reticulonodular shadowing, sometimes with cystic change; upper and mi ddle lobe predominance. May be normal HRCT Diffuse centrilobular nodules, sometimes with ca vitation, and thin and thick-walled cystic lesions, re \202 ecting lesions of varying age. These are interspersed with normal lung. Upper and middle lobe pre- dominance; costophreni c angles are typically spared. Purely nodular or purely cystic appearances may occur. Unusu al manifestations such as single nodules or large airways involvement are also described PF Ts variable, ranging from normal to obstructive, restricted or mixed patterns. Reduced gas transfer and exertional hypoxia are common TBB may yield diagnostic material, although is o ften unhelpful; risk of pneumothorax is unknown although may be increased. Surgical lung bi opsy is often preferable LANGERHANS \200\231 CELL HISTIOCYTOSIS 623 BAL Increased total cell counts and pigmented macrophages, re \202 ecting simply the prese nce of cigarette smoking. Use of antibodies (e.g. OKT6) to detect Langerhans \200\231 cells in BAL \202 uid is limited by poor sensitivity Extrathoracic biopsy of involved sites (e .g. bone) may be diagnostic Diagnosis Usually based on the combination of clinical and HRCT \201 nd- ings: typically a young adult smoker with cysts and nodules on HRCT. Con \201 rmation by surgical lung biopsy may be considered in atypical presentations, such as the \201 nding of solely nodular or cystic disease on HRCT. The appearance of purely cystic dis ease on HRCT may be confused with emphysema (where cysts lack walls) or lymphangioleiomyoma tosis (where cysts are present uniformly in all regions of lung, including the costophrenic angles). Associations \200 Severe pulmonary hypertension \200\224may be seen in the absence of sig- ni \201 cant pare nchymal lung involvement; direct disease involvement of pulmonary vessels has been describe d Manifestations of systemic LCH \200\224particularly diabetes insipidus from pituitary dis ease, skin involvement, lytic bony lesions, and rarely cardiac or gastrointestinal disease Lymphoma \200\224may precede, complicate, or coexist with pulmonary LCH Lung cancer \200 \224more common, probably as a result of cigarette smoking. Management Treatment other than smoking cessation is often not required. Oral corticosteroids may be tried in symptomatic disease, although there is little evidence to support their use; they are usually administe red for at least 6 months. Lung transplantation should be con- sidered in patients with sev ere respiratory failure or pulmonary hyper- tension. Pulmonary LCH may recur in transplante d lungs. Experimental treatments such as the use of IL-2 and anti-TNFA may be of bene \201 t in the systemic forms of LCH seen in children. Prognosis is variable. Spontaneous improv ement is common, although later reactivation of disease may occur. A minority of patients d eterio- rate rapidly with respiratory failure and death within months. Overall life expecta ncy is reduced, with median survival 12 \200\22313 years from diagnosis. Death is most comm only due to respiratory failure. Poor prognostic factors include reduced FEV1, increased re sidual volume, and reduced gas transfer. \200 Further Information Sundar KM et al. Pulmonary Langerhans \200\231 cell histiocytosis. Ches t 2003; 123: 1673 \200\22383 624 CHAPTER 49 Unusual conditions (BOLD) Lymphangioleiomyomatosis (LAM): clinical features De \201 nition and etiology A rare disor der characterized by abnormal proliferation of smooth muscle cells, affecting women of chil d-bearing age, usually in their 30s. The disease is hormone-dependent, so can occur in post -menopausal women on estrogen replacement therapy. \200 \200 \200 \200 Incidence of 1 in 1.1 million population Unknown cause Not hereditary 40% of adult women wi th tuberous sclerosis (learning dif \201 culties, sub- ungal \201 bromas, seizures, faci al angio \201 bromas, autosomal dominant inheritance or spontaneous mutation) develop pulm onary changes identical to those of LAM. Pathology Abnormal proliferation of atypical smooth muscle cells (LAM cells) throughout the lung, airways, blood vessels, and lymphatics. There is nodular in \201 ltration, which is initially subtle. Progressive growth causes lymphatic and airway obstruction, leading to c yst formation throughout the lungs. Clinical features Common \200 Secondary pneumothorax (in two-thirds of patients; occurs due to lung cystic change; recurr ence is common) Dyspnoea (in 42%) Cough (in 20%) Haemoptysis (in 14%) Chylothorax (in 12%, thoracic duct leakage as a result of lymphatic obstruction by LAM cells, may be bilateral). \200 \200 \200 Less common \200 \200 \200 Pleural effusion Chest pain Pulmonary hemorrhage (due to blocked blood vessels and increase d intraluminal pressure). Other organs affected Kidney Angiomyolipoma, a benign tumor, occurs in 50% of LAM patients. Usually diagnosed on CT, these are mostly small and single, but can be mul- tiple and larg er in tuberous sclerosis. Smaller tumors are usually asympto- matic, but larger ones can ca use \202 ank pain and bleeding into the renal tract. Treatment options include tumor rese ction or embolization. Nephrectomy is not usually required. Screening for these lesions is important as it allows careful treatment planning in case they become symptomatic. Abdomen Lymphadenopathy due to lymphatic obstruction. Occurs in one- third of patients and is usually asymptomatic. Pelvis Lymphangioleiomyoma \200\224a cystic mass that enlarges during the day and causes fu llness and bloating. LYMPHANGIOLEIOMYOMATOSIS (LAM): CLINICAL FEATURES 625 Chylous ascites can occur in the absence of chylothorax. Skin Cutaneous swellings, likely due to localized oedema. Examination May be normal. There may be pulmonary crepitations or signs of pleural effusion. Palpable abdominal masses may b e present. Investigations \200 PFTs may be normal, or show a predominantly obstructive pattern. Rarely restrictive. Decrea sed TLCO, with a normal or increased TLC CXR may be normal. Lungs may appear hyperin \202 ated, with reticular shadowing and septal lines due to obstructed lymphatics. There may als o be a diffuse interstitial in \201 ltrate HRCT shows a characteristic appearance, with mu ltiple cysts throughout the lung of varying size, which are usually small (<1 cm) and thin- walled. The adjoining lung parenchyma is normal. There may be pleural effusions. CT abdomen to examine for presence of angiomyolipomas and other lymphatic involvement. 626 CHAPTER 49 Unusual conditions (BOLD) LAM: diagnosis and management Diagnosis Consider particularly in young or middle-aged women with: \200 Recurrent pneumothoraces, especially those with pre-existing dys- pnoea or ha emoptysis Cystic lung disease, air \202 ow obstruction, or chylous pleural effusions Angio myolipomas or other retroperitoneal tumors Tuberous sclerosis and respiratory symptoms \200 \200 The disease is easily missed in its early stages. The diagnosis can be made on the characte ristic CT appearances, or with open lung biopsy. Transbronchial biopsies may not be diagnos tic. Large retroperitoneal abdominal lymph nodes can also be biopsied. Management \200 \200 There are no controlled trials of treatment The course of LAM is variable. Treatment should be aimed at those who are symptomatic and declining Diet Low-fat diet with medium chain tr iglyceride supplementation may prevent chylothorax recurrence, but there is not strong evid ence for this. The diet is dif \201 cult to adhere to Bronchodilators may improve air \202 ow obstruction Hormonal manipulation with progesterone has been tried. It may be bene \201 cial in reducing the decline in FEV1 and TLCO, particularly in patients with progress ive disease, but there are no large studies. Tamoxifen and oophrectomy have also been tried Avoid oestrogens i.e. the oral contraceptive pill and hormone replace- ment therapy Contra ception An increase in symptoms and accelerated disease decline are reported in pregnancy. Use the progesterone-only pill Pleural aspiration when required for pleural effusions. For recurrent effusions or chylothoraces, thoracic duct ligation or pleurectomy may be effectiv e. Pleurodesis can be performed, but this is relatively contra- indicated if future lung tr ansplant is an option Recurrent pneumothoraces Advise regarding \202 ying and diving. Tho racic surgery may be necessary Avoid air travel if possible due to risk of pneumothorax Tra nsplant Single (usually) or double lung, or heart \200\223lung. LAM can recur in the transp lanted lung Stop smoking as this accelerates the rate of decline In \202 uenza vaccine Lia ise with a specialist center if required (this is Nottingham City Hospital in the UK). \200 \200 \200 \200 LAM: DIAGNOSIS AND MANAGEMENT 627 Prognosis is very variable. The condition usually slowly progresses to respiratory failure. At 10 years 55% of patients have MRC grade 3 dysp- noea, 23% are on LTOT, and 10% are hous ebound. Survival: 70% of patients are alive at 10 years, 33% are alive at 15 years, and 25% are alive at 20 years. Future developments Rapamycin may switch off the defect in LAM cell s and prevent their proliferation. Studies are ongoing. Further information Johnson SR, Tatters \201 eld AE. Clinical experience of LAM in the UK. Thorax 2000; 55: 1052 \200\2237 Sullivan EJ. LAM: a review. Chest 1998; 114: 1689 \200\223703 Ryu JH et al. Chylothorax in LAM. Chest 2003; 123(2): 623 \200\2237 628 CHAPTER 49 Unusual conditions (BOLD) Primary ciliary dyskinesia (PCD) A rare genetic cause of chronic respiratory disease, usual ly encountered in adult respiratory clinics as a cause of bronchiectasis. Cilia are found i n: \200 \200 \200 The whole length of the upper respiratory tract Brain ventricles Fallopian tube/ductus epid idymis They are made up of dynein arms, with outer and inner connecting rings, and beat at 14 beat s/s. Many gene defects have been identi \201 ed in PCD, causing a number of cilial abnorma lities. Abnormal cilia do not beat normally, leading to reduced mucociliary clearance, microbiologi cal colonization (which further inhibits cilial action), chronic infection, and the develop ment of bronchiectasis. The main aim following diagnosis in childhood is the prevention of chronic respiratory disease and bronchiectasis. Clinical features \200 \200 \200 Autosomal recessive, >200 phenotypes May present with neonatal respiratory distress Situs i nversus (in about 30%, as cilia determine the side of the organs. Random organ siting occur s with cilial dysfunction, hence the situs inversus of Kartagener \200\231s syndrome) Nasal blockage/rhinitis Persistent wet cough in childhood Hearing problems/history of glue ear/g rommets in childhood Clubbing and signs of chest disease are rare in childhood Wheeze in 20 % Infertility due to immotile sperm (sperm tails have same morphological defect as the cili a and do not beat correctly) In adults the disease usually presents with the clinical signs of bronchi- ectasis: cough productive of purulent sputum, recurrent chest infec- tions, in termittent haemoptysis. \200 \200 \200 \200 \200 Diagnosis Saccharin test (see p 153). Nasal NO is very low in PCD (pos- sibly because NO me diates ciliary function); this is the most sensitive and speci \201 c screening test. Cili al biopsy via the nasal route. Cilia are examined by high-speed digital video, where their beat frequency and pattern can be assessed, con \201 rming the diagnosis. Most cases of PC D are diagnosed in childhood. There is an increased frequency in the children of consanguin - eous marriages. Consider the diagnosis in: \200 \200 \200 \200 Bronchiectasis Situs inversus Persistent upper and lower respiratory infection from early c hildhood Infertility \200\224males may present in infertility clinics. PRIMARY CILIARY DYSKINESIA (PCD) 629 Management A national service for the diagnosis of PCD was set up in 2007, with three cente rs \200\224London (Royal Brompton), Southampton, and Leicester. In adults this involves the treatment of secondary bronchiectasis (see p 154), with: \200 Antibiotics \200 Physiot herapy \200 Vaccinations \200 Management of haemoptysis. 630 CHAPTER 49 Unusual conditions (BOLD) Pulmonary alveolar proteinosis (PAP): pathophysiology and clinical features Pulmonary alveo lar proteinosis (PAP), also referred to as alveolar lipo- proteinosis, is a rare alveolar \201 lling defect affecting around 3 per million people. There is a limited published lite rature: \201 ve reported case series of \211 10 cases, and only 410 total cases reported . Pathophysiology PAP is due to failure of alveolar macrophages to clear spent surfactant, leading to the \201 lling of alveoli with a phospholipid proteinaceous material. It is th ought that the defect has an autoimmune basis, due to the presence of antibodies to granulo cyte-macrophage colony- stimulating factor (GM-CSF), which cause inhibition of normal alveo lar mac- rophage function, leading to abnormalities of surfactant homeostasis. Defects in G M-CSF signaling have been identi \201 ed in animal models. Congenital disease is thought t o be due to mutations in surfactant gene proteins. Other mechanisms for surfactant accumula tion have also been identi \201 ed: \200 Heavy dust exposure leads to surfactant hypersecretion, which exceeds the lungs \200\231 no rmal clearance mechanism. Animal models have shown that this condition develops from endoge nous lipoid pneumonia, with the accumula- tion of lipid-laden macrophages, which break down to release surfactant Amphiphilic drugs e.g. amiodarone, chlorphentermine Lymphoma, leukem ia, and immunosuppression The mechanism is uncertain, but it is thought that the lipoprotei n may be generated from degenerating alveolar cells. \200 Appearances similar to alveolar lipoproteinosis may also be seen in endogenous lipoid pneum onia resulting from bronchial obstruction and are described in surfactant-secreting alveola r cell carcinoma. Histology The alveoli are \201 lled with a granular acellular eosinophi lic PAS (periodic acid \200\223Schiff) positive deposit. Cholesterol clefts and large foamy macrophages may also be seen. The alveolar architecture is usually well preserved. Surfact ant protein can be identi \201 ed using immunohistochem- istry. Electron microscopy shows multiple osmiophilic bodies consistent with denatured surfactant. Epidemiology \200 \200 \200 \200 Presents aged 30 \200\22350 (case reports in children and the elderly) Male to female ratio of 4:1 Increased incidence in smokers Rare familial cases reported. PULMONARY ALVEOLAR PROTEINOSIS (PAP) 631 Clinical features \200 Typically presents with breathlessness and a non-productive cough. Examination may be norma l, or crackles may be heard on auscultation. Clubbing in one-third May present with superad ded infection, causing an apparent acute onset of symptoms in association with fever Median duration of symptoms before diagnosis is 7 months Opportunistic infection is the major com plication, most commonly Nocardia species, fungi, and mycobacteria. This occurs due to impa ired macrophage function and impaired host defense due to surfactant accumulation. \200 632 CHAPTER 49 Unusual conditions (BOLD) PAP: diagnosis and treatment Diagnosis is usually made on the basis of a characteristic CT appearance, although other tests may also be useful. \200 \200 \200 \200 Raised serum LDH ABGs Hypoxia and increased alveolar \200\223arterial (A \200\223a) gradien t PFTs Restrictive defect, with reduced lung volumes and transfer factor CXR Bilateral cons olidation with thickened interlobular septa. Usually bilateral. The pattern is very variabl e, and in up to 50% may be perihilar (bat-wing appearance) CT appearance is characteristic, with airspace shadowing in a geograph- ical distribution, alternating with areas of normal lung, the so-called \200\230crazy paving \200\231 pattern. This CT appearance is not spec i \201 c to alveolar proteinosis, but is also seen in lipoid pneumonia and bronchoalveolar cell carcinoma BAL reveals milky washings. Identi \201 cation of antibodies to granulocyt e- macrophage colony-stimulating factor in BAL washings is diagnostic. Cytological examinat ion shows a granular extracellular deposit with foamy macrophages and cellular debris Trans bronchial/open lung biopsies are occasionally needed if the CT is not characteristic. Treatment of choice is repeated therapeutic whole lung lavage, which should be performed at a specialist center. There are no randomized con- trolled trials of this treatment, but th ere is evidence of ef \201 cacy in terms of subsequent improvement of symptoms, physiology , and radiology. \200 The indication for whole lung lavage is usually breathlessness limiting activities of daily living The procedure is done under general anesthesia using 100% oxygen, and one-lung vent ilation using a double-lumen tube. Repeated warm saline lavage using a closed circuit conti nues until the bronchial washing returns are clear \200\224this may take up to 40 L lavage. One or both lungs may be treated at a time The response is variable \200\224some patients need only one treatment, others may need multiple treatments, and about 10% fail to respond May be done on bypass if the patient is very hypoxic Characteristic milky lavage \202 ui d is obtained. \200 Granulocyte colony-stimulating factor (subcutaneous injections) is a novel treatment option (only phase II studies, no RCT yet), which may prevent progression of disease. There is no bene \201 t from treatment with steroids, and they may exacer- bate opportunistic infections. Prognosis with whole lung lavage is generally good. Spontane ous remis- sion occurs in one-third, one-third remain stable, and one-third progress to res piratory failure and death. There are reports of progression to pul- monary \201 brosis ( which may be a coincidental occurrence). PAP: DIAGNOSIS AND TREATMENT 633 Further information Shah P et al. Pulmonary alveolar proteinosis: clinical aspects and curr ent concepts on pathogenesis. Thorax 2000; 55: 67 \200\22377 Trapnell MD et al. Pulmonary alveolar proteinosis: mechanisms of disease. NEJM 2003; 349: 2 527 \200\22339 634 CHAPTER 49 Unusual conditions (BOLD) Pulmonary arteriovenous malformations (PAVMs): etiology and diagnosis Etiology \200 Pulmonary arteriovenous malformations (PAVMs) are abnormal blood vessels replacing normal c apillaries, making a direct low-resistance con- nection between the pulmonary arterial and systemic venous circula- tions. They vary in size from tiny clusters of vessels (telangiect asia) to larger, more complex aneurysmal-type sacs The disorder is rare, affecting 1 in 15, 000 \200\22324 000 Several genetic susceptibility loci have been identi \201 ed on chromo somes 9 and 12. One identi \201 ed mutation is in the endoglin gene. This modu- lates sign aling via the transforming growth factor-B family of growth factors. This gene is also impl icated in the development of primary pulmonary hypertension Subjects with signi \201 cant PAVMs have low pulmonary vascular resis- tance, a low mean pulmonary artery pressure, and a high cardiac output \200\224due to longstanding adaptive mechanisms to the effects of the shunt, in addition to vascular remodeling effects Most patients present post-puberty, as AV Ms probably develop at this time. They probably grow throughout life, especially during pub erty and in pregnancy. They may rarely regress spontaneously. \200 Diagnosis \200 Most patients present with an abnormal CXR, classically showing a smooth rounded intrapulmo nary mass, with draining or feeding vessels Mild hypoxaemia An AVM is a direct communicatio n between the pulmonary artery and pulmonary vein. Blood therefore bypasses the pulmonary c apillary bed, with reduced oxygenation, which poorly cor- rects with supplementary oxygen O rthodeoxia is desaturation on standing, due to an increase in blood \202 ow in the depend ent lung areas. 70% of PAVMs are basal; hence the desaturation seen CT identi \201 es all AVMs, and can determine those suitable for emboliza- tion. Contrast is not required Patient s may present with the complications of a PAVM, particularly bleeding or peripheral abscess formation. The absence of a normal \201 ltering capillary bed means small particles can reach the systemic circulation, leading to sequelae, particularly in the cerebral circula- tion \200\224strokes and cerebral abscesses. These abnormal vessels are also at risk of rup ture. PULMONARY ARTERIOVENOUS MALFORMATIONS 635 Shunt quanti \201 cation \200 100% oxygen rebreathing study, a non-invasive method of shunt quan- ti \201 cation 99mTC p erfusion scan, a tracer study; the size of the shunt can be assessed from the proportion of radiolabelled macro-aggregates reaching the systemic circulation compared with the total n umber injected. In a normal study, aggregates accumulate in the kidneys Contrast echocardio gram to measure the circulatory transit time of injected echocontrast Angiography at specia list center only In normal individuals the anatomical shunt is <2 \200\2233.5% of the cardi ac output (due to post-pulmonary drainage of bronchial veins into pulmo- nary vein, and dra inage into the left atrium). \200 Clinical features \200 \200 \200 Asymptomatic (50%) Dyspnoea Haemoptysis (10%), probably due to additional bronchial telangi ectasia, which can also cause hemorrhage into bronchi or the pleural cavity Chest pain (12% ); etiology is uncertain Clubbing Cyanosis Orthodeoxia Vascular bruits Telangiectasia; 80% of PAVM patients have hereditary haemorrhagic telangiectasia (HHT), and their families shou ld be screened because of the risk of stroke (see p 618) May present with acute stroke, wit h focal neurological signs \200 \200 \200 \200 \200 636 CHAPTER 49 Unusual conditions (BOLD) PAVMs: management and complications Management Embolization is usually done with coils, whi ch generate local thrombin, leading to cessation of blood \202 ow in AVM feeding vessels. This results in a reduction in the right \200\223left shunt and improvement in hypoxaemia, and should be done by an expert in a specialist center only. The small risk of neurologica l sequelae and angina/arrthymias is reduced with operator experience. 60 \200\22370% of patients are left with a small persisting shunt following treat- ment, an d retain a small risk of abscess formation. Patients are therefore given prophylactic antib iotics for dental and surgical procedures (ensure the patient has a MedicAlert card). Surgi cal resection may be more appropriate than embolization in some cases. Anti-platelet therap y (rarely) in individual cases, if ongoing transient ischaemic attacks. Transplantation is not advised as there is no increased survival bene \201 t over medical treatment. Screenin g The majority of patients with PAVMs have HHT and so screening of family members is import ant. Follow-up All patients need regular follow-up with shunt assessment post- surgical res ection or embolization, as removal of one shunt may unmask or provoke the development of ot hers. Female patients should be advised to defer pregnancy until completion of formal asses sment, because of the risks of growth and rupture of PAVMs in pregnancy (see below). Complications \200 PAVM patients never die of respiratory failure in the absence of addi- tional respiratory d isease All patients are at risk of stroke and cerebral abscesses Transient ischaemic attack /stroke (in 25%) due to rupture of abnormal capillaries in aneurysms Abscess (in 10%) due t o paradoxical emboli through the right to left shunt, and the absence of a \201 ltering c apillary bed \200 Pregnancy is associated with an increase in size of AVMs, and new ones may develop, with po tentially catastrophic consequences. Careful shunt assessment is therefore needed prior to pregnancy, with contraceptive advice prior to specialist assessment. Close liaison between the specialist center and obstetric team is paramount. AVMs may need embolization in the th ird trimester to allow safe delivery. RECURRENT RESPIRATORY PAPILLOMATOSIS 637 Recurrent respiratory papillomatosis These are essentially warts of the upper respiratory t ract, caused by the human papilloma virus (HPV 6 or 11). The virus infects epithelial cells and mucous membranes, similar to that seen in cutaneous and anogenital infection. The infe ction is most commonly acquired during ororespiratory exposure from the mother during vagin al delivery, and typically presents in childhood from 6 months onwards, with signs and symp toms of upper res- piratory tract infection. It may also present for the \201 rst time in adulthood. It is associated with HLA DR3, and with sexual transmission in adults. Recurren t respiratory papillomatosis is rare (2 per 100 000), but oral HPV infection is common. Clinical course This is variable. \200 \200 \200 May remit spontaneously Progressive voice loss and airway obstruction Most cases are con \201 ned to the larynx, although up to 25% of patients subsequently develop extralaryngeal spread to the bronchial tree 1% have malignant change to squamous cell carcinomas Management \200 \200 Surgical excision to maintain airway patency Laser therapy \200\224but potential problems o f thermal injury, stricture for- mation, and spread of papillomas Photodynamic therapy redu ces recurrence rate, using oral or intra- venous photosensitizing agent, then a laser to de stroy photosensitive tissue Microdebrider is now used more commonly Medical treatment \200 \224interferon, aciclovir, ribavirin, isoretinoin, and methotrexate have all been tried \200 \200 Interferon-a as a daily subcutaneous injection leads to complete remission in 30 \200\22350 %, and partial resolution in 30%. One-third recur when treatment is stopped. Adverse reacti ons are common: \202 u-like symptoms, deranged LFTs, leucopenia, and alopecia Cidofovir i s a nucleoside monophosphate analog and inhibits viral polymerase. It is given as an intral esional injection. Potential side- effects include nephrotoxicity and neutropenia. This page intentionally left blank 639 Chapter 50 Upper airway diseases Acute upper airway obstruction 640 Anaphylaxis 642 Upper respiratory tract infections 1 644 Upper respiratory tract infections 2 646 640 CHAPTER 50 Upper airway diseases Acute upper airway obstruction Presentation Sudden respiratory distress with cyanosis and a phonia. Airway obstruction can occur at any level within the airway. Partial airway obstruc tion leads to noisy breathing, with stridor, gurgling, or snoring. Complete airway obstruct ion is associated with distress and marked res- piratory effort, with paradoxical chest and abdominal movement ( \200\230seesaw breathing \200\231), and use of accessory muscles of r espiration. This may be followed by collapse with loss of consciousness, and progress to ca rdio- respiratory arrest. Look for chest and abdominal movements, and listen and feel for a ir \202 ow at the nose and mouth. Causes \200 Pharyngeal occlusion by tongue and other muscles, secondary to loss of muscle tone. This ma y be secondary to drugs, alcohol, a neurological event, or cardiorespiratory arrest Vomit o r blood Inhaled foreign body, which may also cause laryngeal spasm Laryngeal obstruction du e to oedema from burns, in \202 ammation, or anaphylaxis Excessive bronchial secretions, m ucosal oedema, bronchospasm: may cause airway obstruction below the larynx Infection, such as epiglottitis Any cause of chronic airway obstruction, such as an airway tumor or extrins ic compression due to tumor or lymphadenopathy, may dete- riorate precipitously. \200 \200 \200 ACUTE UPPER AIRWAY OBSTRUCTION 641 22 Management of upper airway obstruction Call for senior anesthetic help early \200 Open the airway with backwards head tilt, chin lift, and forward jaw thrust. In cases of tr auma, do not tilt the head, but perform a jaw thrust only If unsuccessful at restoring norm al respiration, visually inspect the mouth for obvious occlusion and remove it with a \201 nger sweep. Leave well- \201 tting dentures in place If there is a witnessed history of choking, consider performing the Heimlich maneuver to dislodge the particle ( \201 rm a nd rapid pressure applied beneath the diaphragm in an upwards movement), or directly visual ize the airway with a laryngoscope and use McGill \200\231s forceps to remove the particle, or with bronchoscope and the use of biopsy forceps If the patient is breathing, consider i nserting an airway to maintain patency: oropharyngeal (Guedel) or nasopharyngeal. Maintain oxy- genation, using mask with reservoir bag, delivering 10 \200\22315 L/min. If there is n o spontaneous respiratory effort, insert a laryngeal mask or endotracheal tube and deliver oxygen via self-in \202 ating bag with supplemental oxygen 10 L/min and reservoir bag. If they are not breathing and cannot be ventilated, a cricothyroidotomy may be necessary (p 76 3) Suction out secretions Maintain circulation with cardiac compression if necessary Seek d e \201 nitive treatment for the cause of airway obstruction, as appropriate. \200 \200 Heliox Helium \200\223oxygen mixtures can be used for patients with airway obstruction, oft en due to tumor compression or invasion. Helium has a lower density than nitrogen and can i mprove ventilation rapidly when used with oxygen. It can be used as an interim measure unti l more de \201 n- itive management is available, such as radiotherapy, or to allow time fo r radiotherapy to take effect. The evidence relating to its use is mainly case studies, wit h no randomized control trials. Nebulized adrenaline may also be helpful in upper airway ob struc- tion, especially laryngeal oedema. This is only a stabilizing measure to buy time un til de \201 nitive treatment is available. 642 CHAPTER 50 Upper airway diseases Anaphylaxis This is a potentially life-threatening medical emergency. Call for help Causes IgE-mediated type 1 hypersensitivity reaction to allergen. Histamine release causes the clinical syndrome. Typical allergens include bee or wasp sting, peanuts, \201 sh, dru gs, foods, latex, contrast media, muscle relaxants, anesthetic agents. Presentation Varying severity of: \200 \200 \200 \200 \200 \200 \200 \200 Angio-oedema Urticaria Dyspnoea Wheeze Stridor Hypotension Arrhythmias Also rhinitis, abdom inal pain, vomiting, diarrhea, sense of impending doom May have had previous episodes of se vere allergic-type reactions. 22 Management of anaphylaxis \200 \200 \200 Remove likely allergen Cardiopulmonary resuscitation if necessary Airway and breathing Admi nister high- \202 ow oxygen through non- rebreathe mask. If airway obstruction present, co nsider tracheal intu- bation. Airway swelling may make this dif \201 cult and cricothyroid otomy may need to be performed (see p 763) Circulation Give adrenaline (epinephrine) IM 1:1 000 solution 0.5 mL (500 g). Repeat after 5 min if no improvement or deterioration In tho se with profound shock and immediately life-threatening anaphylaxis, such as during anesthe sia, or those with no pulse. IV adrenaline can be given slowly, 100 g per min or 1 mL of 1:10 000 solution/min. Stop as soon as there is a response. This can be hazardous and needs cardiac monitoring IV \202 uids if hypotension persists: 1 \200\2232 L rapidly infused A ntihistamines, such as chlorphenamine 10 \200\22320 mg IV Consider steroids: 100 \200\22350 0 mg hydrocortisone IV Consider nebulized salbutamol or adrenaline if bronchospasm On disch arge, provide epipen (IM self-administered adrenaline) and advise on future episodes, Medic Alert bracelet, and card Consider immunology referral if allergen unknown. Consider C1 este rase inhibitor de \201 ciency, especially if repeated episodes. \200 \200 \200 \200 \200 ANAPHYLAXIS 643 Future developments Allergen immunotherapy aiming to desensi- tize to the allergen. Useful in those who cannot avoid allergen exposure. Small amounts of the allergen are injected usu ally weekly, with slowly increasing dose strengths until the maximum dose of the allergen i s admin- istered, which can take up to 12 months. Mechanism unknown, but probably related t o increased IgG binding to the allergen, falling allergen-speci \201 c IgE levels, and dec reased amount of circulating in \202 ammatory cytokines. Can protect against anaphylaxis f or 3 \200\2235 years, but \200\230top-up \200\231 doses necessary. Effective for dust, gra ss, tree, and weed pollen, mold spores, latex, and insect venom, as well as some animal all ergens. Side-effects of administra- tion: anaphylaxis, bronchoconstriction, local reaction. Some centers may not perform in people with chronic asthma because of the risk of death. Further information Abramson M, Puy R et al. Allergen immunotherapy for asthma. Cochrane Da tabase Syst Rev 2003; 4: CD001186 Advanced Life Support Provider Manual, 5th edn, 2006. Resuscitation Council UK 644 CHAPTER 50 Upper airway diseases Upper respiratory tract infections 1 Acute upper respiratory tract infections (URTIs) inclu de rhinitis, pharyn- gitis, tonsillitis, and sinusitis. Upper respiratory tract infections are the commonest cause of people taking time off work i n the United Kingdom. The majority are managed by general practitioners and will not reach a respiratory specialist. They are usually self-limiting and often do not require speci \201 c treatment. Acute rhinitis Nasal congestion with rhinorrhea, mild malaise, and sneezi ng. Most commonly due to viral infection (the common cold). Topical decongestants may be useful. There is no evidence for the use of antibiotics or antihistamines. Candidiasis Oral candida infection is common in those who ha ve received antibiotics, are immunosuppressed, or on oral or inhaled steroids. Seen as whit e plaque-like lesions on the tongue and pharyngeal mucosa. Treat with oral nystatin or amph otericin lozenges, and with oral hygiene. Severe infection can be debilitating, leading to dif \201 culties with eating, espe- cially in the elderly. Exclude underlying immunocompro mise (e.g. HIV, leu- kaemia) in those with persisting infection despite treatment. Acute ep iglottitis (supraglottitis) is infection mainly localized to the epiglottis and surrounding supraglottic structures. It is commoner in children than adults, but a mortality of up to 7% is reported in adults. This is due to upper airways obstruction from grossly oedematous upper airway tissue. \200 