Clues the pneumonia is caused by:

H. influenzae

• Common in smokers and pt with chronic lung dz
• Usually an unencapsulated H. flu = nontypable

Clues the pneumonia is caused by:

Legionella pneumoniae

• Colonizes man-made aquatic systems
• NO human to human transmission
• May be present with high fever, hyponatremia, and diarrhea
• relative bradycardia may also be present
• Sputum: "Abundant PMNs without organisms"
• May appear more ill than the physical exam and CXR would predict
  

Clues the pneumonia is caused by:

Mycoplasma pneumoniae

• Mycoplasma is the smalled, free-living microbe; it has NO cell wall
• Tracheobronchitis is common: the cough is worst at night, persists for 3-4 wks, may see bullous myringitis
• Common in healthy kids and young adults = walking pneumonia
• More common in those < 20 y/o

Clues the pneumonia is caused by:

Chlamydophila pneumoniae

• It's an obligate, intracellular organism = NO gram stain
• Starts as pharyngitis and laryngitis and can move into the LRT to cause cough and pneumonia.
• This means it's easily missed early on
• CXR is very unpredictable, but may show whispy, lower lung opacities without consolidation or effusion

Clues pneumonia is caused by:

Streptococcus pneumoniae

• Acute onset with a single rigor and pleurisy, with tachycardia and tachypnea
• Appears very ill
• 20-30% will have bacteremia
• Empyema is the most common complication
• It's an infected pleural effusion
• S. pneumo is the #1 cause of bacterial pneumonia and it should always be your 1st though

• Irreversible scarring of the lungs caused by inhalation of asbestos fibers
• Sxs: dry, nonproductive cough with gradual onset of DOE.
• Sxs take about 20-40 yrs to arise
• Imaging reveals bilateral pleural plaques with linear opacities
• HRCT is really good at picking this up
• PFTs reveal a restrictive lung pattern

Treatment for pneumoconioses:

Asbestosis

Silicosis

Coal Workers' Pneumoconisis (CWP)

• Smoking cessation
• Smoking + pneumoconisis = increased cancer risk
• Manage respiratory infections
• O2 for hypoxemia
• Control of cor pulmonale (isolated, R ventricular HF in response to a pulmonary issue)

• Diffuse interstitial fibronodular lung dz cause by inhalation of crystalline silica
• TB is accelerated in silicosis pts (30x risk)
• Sxs: DOE, cough with possible sputum production
  

• Lung tissue's reaction to coal dust in the lungs
• Takes about 20-40 yrs for sxs to develop
• Sxs: DOE and cough with sputum, some of which may be black

• A dx of exclusion: no test to +/- it
• Sxs can mimic multiple dzs
• Timing of sxs development: minutes to years
• Sxs:
• Bronchospasm
• BBs, cocaine, IV contrast, NSAIDs, ASA, MDI propellants
• Acute/Subacute Pneumonitis
• Amiodarone
• Pulmonary Fibrosis
• Methotrexate, bleomycin, nitrofurantoin
• Drug-induced Lupus
• Procainamide, hydralazine

Acute/Subacute Pneumonitis

(Drug-Induced Lung Dz)

• Appears days to months after exposure
• Constitutional symptoms with dyspnea and nonproductive cough
• Treat with drug withdrawl, O2 +/- steroids

• Occurs months to years after exposure
• Insidious DOE, pleuritis CP, and non-productive cough
• Need a careful drug hx because of the time lapse between use and dz
• Treat with withdrawl, O2, +/- steroids

• Fever/chills, malaise, pleuritis/effusion, pneumonitis, myalgias/arthralgias
• Tx with drug withdrawl

Hypersensitivity Pneumonitis

"Extrinsic Allergic Alveolitis"

• A constallation of inflammatory lung diseases caused by repeated exposure and immunologic sensitization to organic/chemical agents
• Microbial (bacterial and fungi)
• Malt workers' lung
• Farmer's lung (aspergillosis classically)
• Humidifier fever (pseudomonas, legionella)
• Hot-tub lung
• Animal proteins (avian antigens)
• Bird Fancier's lung
• LMW chemical (isocyanates)
• Sxs: f/c, myalgias, cough, dyspnea 4-12 hrs after exposure
• HRCT: diffuse, ground-glass opacification
• Tx: prevent further exposure; supportive measures plus steroids

Component of a group of systemic disorders that are characterized by vascular wall inflammation and destruction, leading to tissue necrosis. This ultimately results in end-organ dysfunction if left uncontrolled

2 types:

• Diffuse hemorrhage: small vessel involvement; loss of vascular integrity and leakage of blood
• Ex: SLE, Goodpasture's
• Medium to large vessel involvment = inflammation, necrosis, and end organ dysfunction
• GPA

• Caused by diffuse intraalveolar bleeding from small vessels of lungs, particularly alveolar caps
• Classifications:
• Pulm (alveolar) capillaritis
• Essentiall small bessel vasculitis of lungs, which +/- be confined to lungs (ex: SLE)
• Bland alveolar hemorrhage
• A form of DAH in which there is no evidence of alveolar wall inflammation or necrosis, implying cap endotheial injury without inflammation (Ex: Goodpasture's)
• Sxs: hemoptysis (~70%), cough, progressive dyspnea, low-grade fever (depends on amt of bleeding)
• Signs: non-specific pulm findings; but various extrapulm manifs may be present
• CXR: diffuse, patchy alveolar infiltrates
• Tx: find and treat underlying problem

• A pulmonary vasculitis exhibiting a "triad" of s/s: pulmonary hemorrhage, glomerulonephritis, and the presence of anti-glomerular basement membranes
• Believed to be caused by auto-antibodies to antigens found in type 4 collagen of alveolar and clomerular basement membranes
• RFs:
• 20-30 yr olds
• male > female
• may develop after viral UTI, smoking induced, or solvent/hydrocarbon exposure...
• Pulmonary and renal manifestations
• P: "DAH secondary to Goodpasture's"

Granulomatosis with Polyangiitis (GPA)

"Wegener's granulomatosis"

• Most common systemic vasculitis of small and medium aretiers, as well as venules and arterioles
• "Classic GPA" primarily involves upper and lower resp tracts and kidenys (though other places too)
• Upper airway manif (75-90% at presentation)
• Rhinitis (nasal crusting, nosbleeds, nasal septal perforation (saddle-nose deformity)
• hemorrhagic, purulent nasal d/c
• Sinusitis
• Subglottic (trachea/bronchi) stenosis
• Lower Airway manif (45-65%)
• Infiltrates
• Pulmonary nodules (+/- cavitation)
• Alveolar hemorrhage
• Extrapulmonary manif
• Renal (20-60%): glomerulonephritis, proteinuria, renal failure
• Cutaneous (10-25%): usually vasculitis
• Diagnostics
• + C-ANCA (90%)
• increased ESR
• CXR < CT
• Biopsy = Gold Standard!
• Nasal mucosa, lung, kidney - depends on presentation
• Why? B/c the tx is so harsh we want to be positive it's GPA
• Tx: methylprednisonlone (steroid) + cyclophosphamide (chemo) until we've induced remission, then taper doses and maintain.
• TMP-SMX prophylaxis for PCP is common

Churg-Strauss Syndrome

"Allergic Granulomatosis & Angiitis"

• 2nd most common pulmonary vasculidite
• Idiopathic (?autoimmune) multisystem disorder characterized by:
• Allergic rhinitis
• Asthma
• Prominent, persistent, peripheral eosinophilia
• Other sxs: lung > skin > other...
• Phases:
• Prodromal: atopy, allergic rhinitis, asthma; young (20-30 y/o)
• Eosinophilic: periphreal blood and infiltration of multiple organs
• Vasculitic: life-threatening vasculitis of small/medium vessels; fever, wt loss, malaise, lassitude; 30-40 y/o
• Clinical manifestations:
1. Asthma (> 95%); with steroid dependency
2. Nasal/sinus dz: all. rhin., recurrent sinu., nasal polyposis (note: also see in CF)
   
3. Skin dz most commonly a vasculitic presentation; SQ nodules on extensore surface of arms/legs
4. CV dz: commonly HF
5. Neurologic Dz: peripheral neuropathy - mononeuritis multiplex
6. GI dz: eosinophilic gastroenteritis
• Dx
• Peripheral blood eosinophilia
• + P-ANCA (75%)
• increase ESR
• Transient and pathy opacities on imaging
• DX confirmed with tissue bx
• Tx: prednisone
  

• The most common form of ILD/DPLD
• A dx of exclusion
• Characterized by progressive parenchymal scarring and loss of pulm function
• Usually present btwn 50-70 y/o]
• Progressive dyspnea over months-yrs
• Resting or exertional hypoxemia is common
• Chronic, nonproductive cough
• Exam may reveal clubbing and bibasilar fine inspiratory crackles
• PFT = restrictive
• CXR = patchy, ground glass, reticular, or reticulonodular infiltrates
• Infiltrates progress over time
• HRCT is most sensitive: "honey-combing" - thickened collagenous septae surrounding airspaces lined by brinchial epithelium
• Bx is the Gold Standard! - Dx of EXCLUSION

• Tx:
• prednisone + azathioprine; try cyclophosphamide in 3-6 months
• The only proven tx to alter mortality is lung transplant, but most pts aren't candidates
• 3-5 yr median survival once diagnosed

Organizing Pneumonia (OP)

• Pathologic Pattern resulting from organization of an inflammatory exudate in alveolar lumen when resolution of pneumonia doesn't occur
• Characteristic pattern consists of alveolar epithelial injury with pneumocyte necrosis - Intraalveolar buds of granulation tissue develop
• COP (cryptogenic organizing pneumonia) is the most frequent type of OP encountered
• Usually 50-60 y/o
• 70-90% idiopathic: post infections, drugs, CT assoc, etc
• Present with fever, cough, malaise, anorexia, and progressive wt loss
• **sxs usually dvlp subacutely over several wks
• ** dyspnea is usually mild
• Most common PE finding include inspiratory crackles
• PFT = usually mild restrictive
• CXR = multiple, patchy alveolar opacitis, usuallly bilateral, along the periphery
• **desnity of opacities ranges from ground glass to consolidation with air bronchograms
• * may be migratory
• HRCT is especially good
• Bx gives definitive dx: reveals granulation tissue
• Tx:
• prednisone intially with taper over 6 months
• COP may reoccur, esp when triggered by a drug
• TMP-SMZ for PCP prophylaxis common

• Multisystem dz of unknown etiology, characterized by formation of noncaseating granulomas in various organs
• Likely an immune response following specific envir exposure in generticall susceptible pts
• Granulomas contain epithelioid histiocytes surrounded by lumphocytes, plasma cells, and fibroblasts
• Epithelioid cells are transformed bone marrow monocytes that may secrete numerous enzymes - ACE!

• Langerhan's cells are lung dendritic cells almost exclusively intercalated btwn epithelial cells
• PLCH = proliferation and infiltration of lung by LCs, +/- other organ involvement (reactive, not neoplastic process)
• Lung involvement leads to diffuse changes in parenchyma, airway distortion, and recurrent PTX
• Mostly in white (f > m) 20-40 y/o
• Usually in current or former smokers
• "Young, white smoker"
• S/S: dyspnea, productive cough, crackles, wheezes, clubbing
• CXR +/or HRCT:
• Reticulonodular infiltrates mostly prominent in the middle/upper lobes with CPA sparing
• Cystic changes with progression = cystic changes and bullae may be difficult to differ from emphysema
• PFTs = obstructive +/or restrictive = depends on severity
• Lung vol appears normal or increased, which helps distinguish from most other DPLDs
• DLCO usually decreased
• Bx is the Gold Standard
• Tx = smoking cessation +/- prednisone

• Accumulation of the acellular lipoproteinaceous (fatty, protein-like fluid) material in alveolar spaces with minimal interstitial inflammation
• Main problem involves disrupted clearance of surfactant material by alveolar macrophages.
• May be related to impaired action of GM-CSF
• Most are smokers ages 35-40
• Insidious onset (avg 7 mo) of progressive dyspnea and dry cough
• CXR +/- HRCT = bilateral perihilar alveolar infiltrates (w/o evidence of CHF or infection)
• BAL +/or TTBx are Gold Standard Diagnostics
• Tx: whole lung lavage

• Atypical smooth muscle proliferation that results in diffuse custic changes and airway obstruction, recurrent PTX, and chylous effusions
• Most commonly involves the lungs, but others too
• Only 4 things cause chylous effusions: LCA, lymphona, TB, and LAM
• Almost exclusively females 30-40 y/o
• Can differentiate from catamenial PTX because there's an infiltrate on the CXR along with the PTX in LAM
• "Diffuse interstitial infiltration in a non-smoking female of childbearing age with hx/o recurrent PTX +/- chylous effusion"
• Sxs: dyspnea, wheezing, cough, hemoptysis. Minimal signs
• Often "triggered" by some underlying pulm condition:
• spontaneous PTX
• Pulm sxs (dyspnea, wheeze, etc)
• abnormal CXR
• CXR: minimal early on; advanced: reticulonodular densities -> cystic changes with sings of hyperinfiltration
• HRCT: advanced dz reveals diffuse cystic changes with no sparing of CPAs
• PFT is variable, depending on smoking hx
• Bx is the Gold Standard Diagnostic
• Tx: supportive (PTX, effusion), ?estrogen antagonist, ?transplant

Genetically controlled switch from mold form at ambient temperature to yeast form at body temperature

"Switch hitters"

• H. capsulatum
• B. dermatitidis
• S. schenckii

1.  Hematologic malignancies (lymphoma, leukemia)
2. BMT and solid organ transplant pts
3. Anyone on corticosteroids (prednisone) or other immunosuppressive agents (infliximab)
4. AIDS pts
   

• "Old" agents:
• Amphotericin B (IV)
• Too toxic (SEs), but works really well
• New agents:
• Amphotericin B lipid complex
• Amphotericin B cholesteryl sulfate
• Amphotericin B liposomal
• We "wrapped it in fat" and made it more "accessable" and with fewer SEs: less f/c, ARF, electrolyte abnorms. (More effective than conventional Amphotericin B)
• **On restriction - only ID specialist can order this

• "Old" agents
• Itraconazole
• "New"
• Fluconazole
• Voriconazole
• Posaconazole

• Caspofungin
• Micafungin
• Anidulafungin

• Filamentous fungus with septate hyphae, branching at about 45* angle; A. fumigatus is the most common cause of invasive dz
• Found most frequently in soil, water, and decaying vegetation
• Assoc with hospital constru ction work or contaminated ventilation systems
• No person-to-person transmission
• Generally inhaled, settling in the sinus (U) and lungs (L).
• The hyphae invade the tissue with a particular propensity for angioinvasion = hemorrhagic infarction and necrosis of involved tissue. Erosin into the tissue leads to hemoptysis
• 3 types of infection
1. Invasive Aspergillosis
2. Aspergilloma
3. Allergic Bronchopulmonary Aspergillosis

• Risk factors:
• Isially in pts with hematological maligs and BMT recips, with a 60-90% mortality rate
• Prolonged neutropenia (ANC < 100) is the greatest risk factor = very, very immunosuppressed pts
• Clinical Manifs
• Asymptomatic -> fever, nonproductive cough, dyspnea, CP
• Hemoptysis in the appropriate host = aspergillosis
• Dx with culture and imaging
• Culture resp secretions and biopsy tissue
• note that in very immunosuppressed pts, bx is not possible because the procedure (Bronch) is very high risk
• Nodular cavitary lesion on CXR or a zone of low attenuation around a mass "halo sign" on chest CT
• Tx: refer; high dose steroids

• Fungus ball = Saprophyte, a colonizer that's not invading, just living in that spot
• Heavy Aspergillus colonization of a preexisting cavity
• Risk factors:
• Underlying cavitary lung dz (ie: COPD) common
• Dx: sputum/tissue culture & imaging
• CXR may show fungus ball with an air crescent sign
• Looks like a tumor, so look for the crescent (but not always there) = work up as a tumor until proven otherwise
• Tx: individualized
• Surgical excision +/- itraconazole or voriconazole
• If surgically excised, aren't going to need to tx with antifungals since you removed it (?)

• An allergic dz; probably represent a hyperimmune rxn (exaggered T-cell response) to Aspergillus organism rather than a true infection.
• Risk factor = underlying asthma condition (allergic) or CF pts
• Clin manifs
• Worsening asthma that is difficult to control AND
• Cough productive of thick, brownish plugs of sputum AND
• Peripheral eosinophilia + very high plasma [IgE]
• Tx: itraconazole +/- corticosteroids

• Crytpocossus neoformans; encapsulated, yeast-like fungus that reproduced by pudding
• Worldwide; found primarily in pigeon droppings
• Usually acquired at an early age via inhalation
• Risk factors: Depends on presentation:
• Pulmonary:
• Immunocompetent & immunosuppressed
• Suppressed - breaks through the lungs and goes out - loves to move to the CNS
• CNS or Disseminated:
• Primarily AIDS pt (CD4 <50-100)
• This is considered an AIDS defining illness
• Pts on immunosuppressive tx (prednisone, transplant meds, TNF-α inhibitors)
• Clin Manifs
• Pulmonary: may cause pneumonia: looks like CAP but won't respond to ABX
• CNS: chronic meningitis: presents like bacterial meningitis (takes days to weeks) but generally without fever and is more subtle
• Neck pain, fatigue, myalgias, photo/oto phobias, some plaseys, HA
• The sxs are subtle because this happens in immunosuppressed, who don't have an immunesystem to generate a response that leads to sxs. Veryrare to see this in immunocompetent
• Dx:
• CXR/CT -> BAL +/- TBBx
• Serum cryptococcal antigen test (sensitivity > 90%)
• Tx:
• Pulmonary: fluconazole x 6-12 mo
• CNS/Disseminated: refer

• Coccidioides immitis: endemic mycosis, dimorphic fungi. It's generally inhaled.
• Risk factor: history of at least transient travel to an endemic area (it normally inhabits soil in the desert of SW US)
• Clin Manifs - various levels of severity
• 60% of cases are asymptomatic (breathed in a little)
• Most common clinical manifestation is a flu-like illness for 1-2 weeks
• Episodes of fever, arthralgia, erythema nodosum (red patch with underlying nodules on the anterior tibia), and erythema multiforme
• Hypersensitivity phenomena to primary infection = "desert rheumatism"
• Pneumonia is the most common serious presentation: CAP-like pattern to TB-like pattern
• Dx:
• IgM and IgG
• Histopathology with fungal stain/culture
• Tx:
• Primary pulmonary (pts at low risk for persistence/complications)
• Antifungals generally not recommended -> tx if fever, wt. loss, +/or fatigue don't resolve within 2-8 wks
• Itraconazole or fluconazole for mild-mod dz for 3-12 months
• Refer for severe dz

• Histoplasma capsulatum: endemic mycosis, dimorphic fungi. Generally inhaled. Most common fungal infection in the US.
• Risk factors:
• Exposure: anyone who has contact with animals, droppings, soil - work outside, construction, demolition, farmer/gardner, micro lab, restoration, roofer, spelunker, etc
• Risk for dissemination increases with defect in CMI = most commonly AIDS pts
• History of at least transient exposure to endemic areas OR exposure to avian excreta or bat guano.
• Clinical Manifs
• Acute Primary Histoplasmosis
• Fibrosing Mediastinitis
• Disseminated Histoplasmosis
• Dx:
• CXR: bilateral fuzziness more likely a fungal or atypical process. Calcified nodules are almost pathognomonic for histo
• Antigen detenction: assy may be applied to serum, urine, CSF
• Histopathological examination - usually BMBx
• Fungal BICx
• Tx:
• All tx considerationa depend on patient characteristics and clinical manifestation
• Refer all cases

• > 95% of people will develop an asymptomatic infection or an illness so mild it may be misdiagnoses as a URTI (as long as CMI is normal)
• Those with high-inoculum exposure or with defects in CMI may develop an acture pulmonary infection
• Usually the immune system (CMI) contains the infection, often with granuloma formation and healing with calcification -> "SPNs"
  

• Hyperintense fibrotic reaction of the mediastinum may occur after acute pneumonitis
• Most common cause, other than malignancy (small cell), of superior vena cava syndrome
• Hinders flow from UEs, head, etc to the heart
  

• Mainly in pts with defects in CMI
• Presentation variable-TB like
• Note: Histo is very TB like - has the ability to infect many different organs

• Blastomyces dermatitidis: endemic mycosis, dimorphic fungi. Generally inhaled. "Histo's kissing cousin"
• In soil with large amounts of organic debris/animal excreta
• Around the Great Lakes region and Ohio River Valley
• Risk Factors:
• Common in those who work outside or who engage in activity along
• "Uncommon" in immunocompromised pts/AIDS: ie: just as likely in immunocompetent as in immunocompromised - no difference in risk
• Clinical Manifs
• Pulmonary Blastomycosis
• Cutaneous Blastomycosis
• Dx:
• Urinary antigen
• Direct examination of samples with KOH prep
• Tissue bx with histological stain and fungal stain/culture
• Tx: refer!

• Acute pulmonary infections resemble bacterial pneumonia
• 50% asymptomatic
• Consider if pt has risk factors & has CAP that doesn't respond to routine ABX (similar to cryptococcus)
  
• Chronic pulmonary infections resemble TB

• Generally implies disseminated dz
• Papules or pustules - verrucous (fungating, heaped up) or ulcerative lesions
• May be solitary or multiple and with or without pulmonary findings
• 40% of pts present with skin lesions
• Note: disseminated doesn't mean the pt is immunosuppressed, it can happen in anyone.

• Pneumocystis jiroveci, fungus. Likely transmitted by aerosolized secretions from human hosts - Not reactivation of latent infection.
• Risk factors
• AIDS pts with CD4 < 200
• Considered an AIDS-defining illness
• Immunocompromised pts (high-dose steroids)
• Clin Manifs
• Sxs develop subacutely over weeks (2-4 avg)
• Persistent fever, nonproductive cough, & wt loss
• Immune system is amped up - causes anorexia over those weeks, maybe 10 lbs lost
• SOB (esp DOE) occurs late in dz
• 50% of pts will have normal pulm examinations
• They look sicker than their exam suggests: probably be on high-flow O2, look like crap, may be on bipap, but will have clear auscultation
• Dx:
• Serum LDH elevated
• CXR pattern diffuse bilateral interstitial infiltrates: "ground glass" appearance
• Sputum for IFA: 70-90% sensitive (stains not recommended)
• Gold Standard Diagnosis is BAL - sent for IFA (90% sensitive)
• TMP-SMX is the Gold Standard is prophylaxis
• Tx:
• IV TMP-SMX is the gold standard
• Add prednisone taper over 21 d for pts witha PaO2 < 70 mmHg or A-a gradient > 35 mmHg